Quality of life in children with congenital heart defects

PURPOSE: The antiepileptic effects of zonisamide (ZNS) have been well documented experimentally and clinically. The purpose of this study was to examine whether ZNS reduces cerebral damage after transient focal ischemia in rats. METHODS: Ischemia was induced by a transient occlusion of the left middle cerebral artery (MCA) with a 3-0 nylon monofilament for 90 min. Neurological evaluation was performed by measuring the event of neurological deficit of the contralateral forepaw and hindpaw at 10 min and 1 day after MCA occlusion (MCAo). Brain infarct size was determined by measuring triphenyltetrazonium chloride-negative stained area of the serial brain sections 1 day after MCAo. RESULTS: The pre- or postischemic treatment with ZNS [(10-100 mg/kg p.o.), 30 min before and 4 h after or 15 min and 4 h after the occlusion] markedly reduced cerebral damage in the ipsilateral hemisphere and the neurological deficit induced by transient ischemia. The reducing effect on the damage was observed in the cortical and subcortical regions. Preischemic treatment with carbamazepine (CBZ 60 mg/kg p.o. twice 30 min before and 4 h after MCAo) tended to reduce the cerebral damage and neurological deficit, but the lower dose (20 mg/kg p.o. twice) did not. Valproate (VPA 1,000 mg/kg p.o. twice) also had no effect. CONCLUSIONS: ZNS at the anticonvulsant dose, unlike CBZ and VPA, ameliorated the brain infarction and the event of neurological deficit after transient focal cerebral ischemia. These data suggest that ZNS has therapeutic potential in protecting against ischemic cerebral damage, such as stroke.     

Impulsive and compulsive self-injurious behavior in bulimia nervosa: prevalence and psychological correlates

Acute ischemia in the complete territory of the carotid or the middle cerebral artery may lead to cerebral edema with raised intracranial pressure and progression to coma and death. Although clinical data suggest benefit for patients undergoing decompressive surgery for massive space occupying hemispheric stroke, little data about the effects of this procedure on morbidity and outcome is available. The experimental data support an early surgical approach. For early and probably most effective treatment of severe, space-occupying cerebral ischemia, the "malignant" character of the brain edema has to be recognized early after onset of vessel occlusion. Hereby magnetic resonance imaging (MRI) may allow to determine the clinical significance of brain edema early after onset, simultaneously allowing to monitor the evolution of ischemia. We performed serial SE-MRI in rats with acute hemispheric infarctions treated by decompressive craniectomy. Focal cerebral ischemia was induced in 36 rats using an endovascular occlusion technique. Decompressive craniectomy was performed 4 and 24 hours after vessel occlusion in groups of 12 animals each. Twelve animals were not treated by decompressive craniectomy (control group). Four, 24, 48, 72 and 168 hours after MCAO all animals were examined with conventional T1- and T2-weighted SE-MRI. Shift of the midline structures and compression of the ventricles were scored. Changes in weight and neurological performance were measured daily. The infarction volume was calculated by triphenyltetrazolium chloride staining 168 hours after MCAO. While mortality in the untreated group was 33.3%, none of the animals treated by a decompressive craniectomy died (mortality 0%). Neurological behaviour, weight loss and infarction volume were significantly better in the animals treated by early decompressive craniectomy (p < 0.05). Four hours after MCAO all untreated animals showed a massive shift of the midline structures and a massive compression of the ventricles; only 7 of 12 animals treated early by craniectomy showed mild mass effects. Correlation of the histological brain damage with T2-weighted MRI 4 hours after MCAO was poor (r = 0.41); later than 24 hours there was a good correlation (r > 0.7). Our results suggest that decompressive craniectomy in malignant cerebral ischemia reduces mortality and significantly improves outcome. If performed early after vessel occlusion, it also significantly reduces infarction size. In the acute phase of hemispheric infarction conventional SE-MRI is not sensitive in estimation of infarction size. Later than 24 hours, conventinal SE-MRI proved to be useful in monitoring brain edema and infarction size in this rat model of malignant hemispheric stroke.     

Glucose plus insulin infusion improves cerebral outcome after asphyxial cardiac arrest

Hyperglycemia before ischemia worsens cerebral outcome. The aim of this study was to determine the cerebral effects of giving glucose with or without insulin after asphyxial cardiac arrest. Rats underwent 8 min of asphyxial cardiac arrest. After arrest, Group 1 received NaCl; Group 2, insulin; Group 3, glucose; and Group 4, glucose plus insulin, all intravenously. Neurological deficit (ND) scores were 14+/-10%, 22+/-12%, 12+/-10% and 2+/-2% in Groups 1-4, respectively, 72 h after reperfusion. Overall histological damage (HD) scores were 4, 2, 3 and 1, respectively. Group 4 fared significantly better than group 1 on both scores. Glucose after asphyxial cardiac arrest in rats produces no increased brain damage while glucose plus insulin improves cerebral outcome.     

Brain mu-calpain autolysis during global cerebral ischemia

Proteolytic degradation of numerous calpain substrates, including cytoskeletal and regulatory proteins, has been observed during brain ischemia and reperfusion. In addition, calpain inhibitors have been shown to decrease degradation of these proteins and decrease postischemic neuronal death. Although these observations support the inference of a role for mu-calpain in the pathophysiology of ischemic neuronal injury, the evidence is indirect. A direct indicator of mu-calpain proteolytic activity is autolysis of its 80-kDa catalytic subunit, and therefore we examined the mu-calpain catalytic subunit for evidence of autolysis during cerebral ischemia. Rabbit brain homogenates obtained after 0, 5, 10, and 20 min of cardiac arrest were electrophoresed and immunoblotted with a monoclonal antibody specific to the mu-calpain catalytic subunit. In nonischemic brain homogenates the antibody identified an 80-kDa band, which migrated identically with purified mu-calpain, and faint 78- and 76-kDa bands, which represent autolyzed forms of the 80-kDa subunit. The average density of the 80-kDa band decreased by 25 +/- 4 (p = 0.008) and 28 +/- 9% (p = 0.004) after 10 and 20 min of cardiac arrest, respectively, whereas the average density of the 78-kDa band increased by 111 +/- 50% (p = 0.02) after 20 min of cardiac arrest. No significant change in the density of the 76-kDa band was detected. These results provide direct evidence for autolysis of brain mu-calpain during cerebral ischemia. Further work is needed to characterize the extent, duration, and localization of mu-calpain activity during brain ischemia and reperfusion as well as its role in the causal pathway of postischemic neuronal injury.     

Normoxic ventilation after cardiac arrest reduces oxidation of brain lipids and improves neurological outcome

BACKGROUND AND PURPOSE: Increasing evidence that oxidative stress contributes to delayed neuronal death after global cerebral ischemia has led to reconsideration of the prolonged use of 100% ventilatory O2 following resuscitation from cardiac arrest. This study determined the temporal course of oxidation of brain fatty acyl groups in a clinically relevant canine model of cardiac arrest and resuscitation and tested the hypothesis that postischemic ventilation with 21% inspired O2, rather than 100% O2, results in reduced levels of oxidized brain lipids and decreased neurological impairment. METHODS: Neurological deficit scoring and high performance liquid chromatography measurement of fatty acyl lipid oxidation were used in an established canine model using 10 minutes of cardiac arrest followed by resuscitation with different ventilatory oxygenation protocols and restoration of spontaneous circulation for 30 minutes to 24 hours. RESULTS: Significant increases in frontal cortex lipid oxidation occurred after 10 minutes of cardiac arrest alone with no reperfusion and after reperfusion for 30 minutes, 2 hours, and 24 hours (relative total 235-nm absorbing peak areas=7.1+/-0.7 SE, 17.3+/-2.7, 14.2+/-3.2, 16.1+/-1.0, and 14.0+/-0.8, respectively; n=4, P<0.05). The predominant oxidized lipids were identified by gas chromatography/mass spectrometry as 13- and 9-hydroxyoctadecadienoic acids (13- and 9-HODE). Animals ventilated on 21% to 30% O2 versus 100% O2 for the first hour after resuscitation exhibited significantly lower levels of total and specific oxidized lipids in the frontal cortex (1.7+/-0.1 versus 3.12+/-0.78 microg 13-HODE/g wet wt cortex., n=4 to 6, P<0.05) and lower neurological deficit scores (45.1+/-3.6 versus 58.3+/-3.8, n=9, P<0.05). CONCLUSIONS: With a clinically relevant canine model of 10 minutes of cardiac arrest, resuscitation with 21% versus 100% inspired O2 resulted in lower levels of oxidized brain lipids and improved neurological outcome measured after 24 hours of reperfusion. This study casts further doubt on the appropriateness of present guidelines that recommend the indiscriminate use of 100% ventilatory O2 for undefined periods during and after resuscitation from cardiac arrest.     

Neither L-arginine nor L-NAME affects neurological outcome after global ischemia in cats

BACKGROUND AND PURPOSE: We attempted to determine whether N-nitro-L-arginine methyl ester (L-NAME) would improve neurological outcome and whether L-arginine (L-ARG) would worsen neurological outcome after transient global ischemia. METHODS: Halothane-anesthetized cats (n = 6 for each group) were treated with intravenous saline, L-NAME (5 mg/kg or 10 mg/kg), or L-arginine (300 mg/kg) 30 minutes before 10 minutes of ischemia (temporary ligation of the left subclavian and brachiocephalic arteries with hemorrhagic hypotension to 50 mm Hg). At 30 minutes of reperfusion, cats in the L-ARG group were administered an additional 300 mg/kg dose of intravenous L-arginine. RESULTS: Time (mean +/- SE) to isoelectric electroencephalography was similar among groups (saline, 26 +/- 11 seconds; L-NAME-5, 15 +/- 4 seconds; L-NAME-10, 36 +/- 27 seconds; and L-ARG, 22 +/- 7 seconds). At 72 hours, reperfusion pathological injury was severe and neurological deficit score (mean, range) was similar among groups (saline, 38[11 to 70]; L-NAME-5, 52 [40 to 73]; L-NAME-10, 47 [23 to 70]; and L-ARG, 40 [0 to 79]). CONCLUSIONS: Nitric oxide is not important in the mechanism of brain injury after global ischemia in cats.     

Mortality among workers in the pulp-paper industry. A successive follow up of the cohort

Neuropathologic findings are described, for the first time, in a neonatal dog model of circulatory arrest in normothermic conditions, and the findings are compared to those reported in neonatal dogs with hypothermic circulatory arrest. Total circulatory arrest was produced in 3- to 6-day-old anesthetized, paralyzed and ventilated, normothermic dogs either by asphyxiation or cardioplegia. Duration of circulatory arrest was 8-20 min and 10-40 min in asphyxiated and cardioplegic animals, respectively. The animals were resuscitated and maintained under controlled systemic physiologic conditions until neuropathologic examination after 8 or 24 h of recovery. The results suggest that the minimal durations of circulatory arrest for brain damage to occur following asphyxia or cardioplegia are 10 and 15 min, respectively. Ischemic lesions in both groups consisted of neuronal necrosis and involved mainly the brain stem structures, particularly the reticular nuclei and the spinal cord gray matter. The medulla was more severely involved than midbrain and pons. There was a direct correlation between the length of circulatory arrest and the severity of damage in the medulla (P = 0.001) and overall brain stem damage (P = 0.004) in animals with cardioplegia, but not in animals with asphyxia. These findings are compared to the neuropathologic changes previously described in newborn dogs subjected to hypothermic circulatory arrest, in which ischemic lesions are focused on the cerebral cortex and basal ganglia. It is concluded that hypothermia in this model not only prolongs the period of circulatory arrest that is required to produce brain damage, but also shifts the pattern of regional ischemic vulnerability from caudal to more rostral structures.     

Failures in information processing in patients with Korsakoff''s syndrome

By means of a modified and simplified surgical and implantation technique, standardized values for visually evoked potentials (EP) from 7 brain structures (caudate nucleus, posterior hypothalamus, mesencephalic reticular formation, intra-laminar thalamic nuclei, amygdala, dorsal hippocampus and visual cortex) are obtained. The importance of a careful selection of the animal material, constant test conditions and the selection of test parameters as a prerequisite for the assessment of psychotropic drugs is emphasized and discussed. As an example of the specific influence on visually evoked potentials in the above named brain structures, the effects of haloperidol and amytriptyline on latencies and amplitudes of the individual parameters of EPs are described. It is assumed that the method described can be of great assistance for investigation and classification of newly developed substances.     

Concentration dependence of sodium permeation and sodium ion interactions in the cyclic AMP-gated channels of mammalian olfactory receptor neurons

We explored the hypothesis that brain damage after cardiac arrest caused by ventricular fibrillation (VF) needs different therapies than that after asphyxiation, which has been studied less thoroughly. In 67 healthy mongrel dogs of both sexes cardiac arrest (at normothermia) by ventricular fibrillation (no blood flow lasting 10 min) or asphyxiation (no blood flow lasting 7 min) was reversed by normothermic external cardiopulmonary resuscitation, followed by intermittent positive-pressure ventilation for 20 h, and intensive care to 96 h. To ameliorate ischemic brain damage, the calcium entry blocker lidoflazine or a solution of free radical scavengers (mannitol and L-methionine in dextran 40) plus magnesium sulphate, was given intravenously immediately upon restoration of spontaneous circulation. Outcome was evaluated as functional deficit, brain creatine kinase (CK) leakage into the cerebrospinal fluid (CSF) and brain morphologic changes. Lidoflazine seemed to improve cerebral outcome after VF but not after asphyxiation. Free radical scavengers plus magnesium sulphate seemed to improve cerebral outcome after asphyxiation, but not after VF. After VF, scattered ischemic neuronal changes in multiple brain regions dominated, and total brain histopathologic damage scores correlated with final neurologic deficit scores at 96 h (r = 0.66) and with peak CK levels in CSF (r = 0.81). After asphyxiation, in addition to the same ischemic neuronal changes, microinfarcts occurred, and there was no correlation between total brain histopathologic damage scores and neurologic deficit scores or CK levels in CSF. CONCLUSIONS: Different mechanisms of cardiac arrest, which cause different morphologic patterns of brain damage, may need different cerebral resuscitation treatments.     

One-stage repair of interrupted aortic arch with selective cerebral perfusion

To minimize the neurological compromise after the circulatory arrest, the selective cerebral perfusion could be beneficial. We underwent one-stage repair of the interrupted aortic arch (IAA) with various intracardiac anomalies for the six patients, age ranging from 12 days to 4 months, by using the selective cerebral perfusion. Cardiopulmonary bypass was established by using two-way arterial cannulation supported by the two respective pump systems, one of which utilized the EPTFE graft anastmosed to either the bracheocephalic artery or the right subclavian artery and second of which enrouted through the arterial ductus to the descending aorta. The cerebral perfusion during the circulatory arrest for the aortic arch repair was maintained by the selective perfusion via EPTFE graft with 10 ml/kg/min blood flow. After the completion of the arch repair, the total system perfusion was restarted through the graft and the repair of the intracardiac anomalies was followed. Of six, no operative death or neurological complications related to the operation were found. The clinical neurological evaluation after operation also demonstrated the normal for the age. In conclusion, the selective cerebral perfusion by using the EPTFE graft during the circulatory arrest might decrease the risk of brain damage.     

Electrophysiological (EEG-SSEP) monitoring during middle cerebral aneurysm surgery

SSEPs were monitored during 38 procedures for aneurysms of the middle cerebral artery. In 13 selected patients intraoperative barbiturate protection with sodium thiopental was performed during temporary M1 occlusion. Combined EEG monitoring, showing burst suppression typical pattern of electrical cortical activity, allows a minimal dosage (3-6.5 mg/kg) of thiopental to achieve brain protection. Any patient with TYPE I SSEP changes had a new postoperative neurological deficit. Five patients during temporary middle cerebral artery clipping showed TYPE II SSEP changes and only one, not achieving burst suppression EEG pattern, had transient postoperative neurological deficit. In two other patients, a progressive worsening of TYPE II SSEP was observed; this was due to excessive brain retraction without brain protection and had a prolonged postoperative neurological deficit. Four patients showed TYPE IV SSEP changes during temporary M1 occlusion, one of whom was a 52-year-old woman, who, in spite of brain protection with thiopental, had serious postoperative neurological sequelae. In this patient N20 amplitude and central conduction time did not have full recovery to the preocclusive values. This study suggests that combined electrophysiological monitoring may reduce complications due to excessive retraction of cerebral tissue, make temporary clipping safer and improve the results of middle cerebral artery aneurysm surgery.     

Cerebral physiology in paediatric cardiopulmonary bypass

PURPOSE: To analyze studies of neurological injury after open-heart surgery in infants and children and to discuss the effects of cardiopulmonary bypass, hypothermia and deep hypothermic circulatory arrest on cerebral blood flow, cerebral metabolism and brain temperature. SOURCE: Articles were obtained from the databases, Current Science and Medline, from 1966 to present. Search terms include cardiopulmonary bypass (CPB), hypothermia, cerebral blood flow (CBF), cerebral metabolism and brain temperature. Information and abstracts obtained from meetings on the topic of brain and cardiac surgery helped complete the collection of information. PRINCIPAL FINDINGS: In adults the incidence of neurological morbidity is between 7 to 87% with stroke in about 2-5%, whereas the incidence of neurological morbidity increases to 30% in infants and children undergoing cardiopulmonary bypass. Besides the medical condition of the patient, postoperative cerebral dysfunction and neuronal ischaemia associated with cardiac surgery in infants and small children are a combination of intraoperative factors. Deep hypothermic circulatory arrest impairs CBF and cerebral metabolism even after termination of CPB. Inadequate and/or non-homogenous cooling of the brain before circulatory arrest, as well as excessive rewarming of the brain during reperfusion are also major contributory factors. CONCLUSION: Newer strategies, including the use of low-flow CPB, pulsatile CPB, pH-stat acid-base management and a cold reperfusion, are being explored to ensure better cerebral protection. Advances in monitoring technology and better understanding of the relationship of cerebral blood flow and metabolism during the different modalities of cardiopulmonary bypass management will help in the medical and anaesthetic development of strategies to improve neurological and developmental outcomes.     

Morphological and pharmacological evidence for the existence of brain regulatory circuits in the immune response

Muramyl dipeptide (MDP) has a variety of biological effects including the effect on CNS, such a promotion of sleep, fever, analgesic effect or some behavioural changes and of course a very potent effect on immune system. The latter effect is at least partly mediated through the structure in CNS. With the small electrolytic lesions which were placed in brain from the spinal cord through the brain stem up to the cerebral cortex we have identified a number of structures such as medial frontal cortex (area Cg1-Cg3), subnucleus basomedialis and centralis of amygdala, subnucleus medialis and dorsolateralis of nucleus parabrachialis, lateral part of reticular formation (monoaminergic groups A1-7) and the part of the reticular formation (serotonergic groups B6-B8) which are evidently involved in the immunomodulatory and immunoadjuvant effect of muramyl dipeptide. The results of experiments also suggest that the interaction between neuroendocrine and immune systems might take place on the level of some of above mentioned anatomical structures.     

Age-related differences in the effect of dichloroacetate on postischemic lactate and acid clearance measured in vivo using magnetic resonance spectroscopy and microdialysis

Numerous studies using adult animal models suggest that dichloroacetate (DCA) may have neuroprotective properties by virtue of its ability to increase rates of metabolism and, therefore, clearance of brain lactic acidosis, which may accumulate during cerebral ischemia. We tested the hypothesis that postischemic DCA administration affects lactate and acid clearance to different extents in immature versus mature brain. 31P and 1H magnetic resonance spectroscopy were used to measure intracellular acid and lactate clearance rates in vivo in newborn and 1-month-old swine after a 14-min episode of transient near-complete global ischemia. Simultaneous monitoring of extracellular lactate efflux and clearance was measured in the same animals by in vivo microdialysis. Plasma glucose concentrations were elevated in order to study animals with severe cerebral lactic acidosis. Maximal levels of brain lactosis (16-20 micromol/g) and acidosis (PHintracellular 5.8-6.0) were reached during the first 10 min of recovery and were the same in age groups and in subgroups either acting as controls or treated with DCA (200 mg/kg) given from the last minute of ischemia to 5-7 min after ischemia. For newborns, DCA administration improved the postischemic clearance rate of cerebral acidosis and cerebral phosphocreatine, with similar trends for the clearance of lactosis and increased rates of recovery of nucleotide triphosphates, compared with controls. In contrast, DCA administration in 1-month-olds resulted in a modest trend for improvement of cerebral lactate clearance, but did not affect acid clearance or the recovery rate of phosphocreatine or nucleotide triphosphates. Extracellular brain lactate concentrations had similar relative increases and rates of decline for subgroups of either age treated with DCA versus controls. The results of this study indicate that postischemic DCA administration helps to resolve cerebral acidosis to a greater degree in immature than more mature brain, suggesting that DCA may have cerebroprotective properties for neonatal hypoxic-ischemic encephalopathy.     

Lidocaine prolongs the safe duration of circulatory arrest during deep hypothermia in dogs

PURPOSE: To test the hypothesis that lidocaine prolongs the safe period of circulatory arrest during deep hypothermia. METHODS: Sixteen dogs were subjected to cooling, first surface cooling to 30 degrees C and then core cooling to 20 degrees C rectal temperature). The circulation was then stopped for 90 min. In the lidocaine group, 4 mg.kg-1 lidocaine was injected into the oxygenator two minutes before circulatory arrest and 2 mg.kg-1 at the beginning of reperfusion and rewarming. The control group received equivalent volumes of normal saline. Post-operatively, using a neurological deficit scoring system (maximum deficit score-100; minimum-zero indicating that no scored deficit could be detected). Neurological function was evaluated hourly for six hours and then daily for one week, the pharmacokinetic parameters were calculated using one compartment model. RESULTS: On the seventh day, the neurological deficit score and overall performance were better in the lidocaine (0.83 +/- 2.04) than in the control group (8.33 +/- 4.08 P < 0.05). During the experiment, the base excess values were also better in the lidocaine than in the control group (at 30 min reperfusion: -4.24 +/- 1.30 vs -8.20 +/- 2.82 P < 0.01, at 60 min reperfusion was -3.34 +/- 1.87 vs -7.52 +/- 2.40 (P < 0.01). On the eighth day the extent of pathological changes were milder in the lidocaine group than that in the control group. The elimination half life of lidocaine was 40.44 +/- 7.99 during hypothermia and 2.01 +/- 4.56 during rewarming. CONCLUSIONS: In dogs lidocaine prolongs the safe duration of circulatory arrest during hypothermia.     

Comparison of brain tissue metabolic changes during ischemia at 35 degrees and 18 degrees C

BACKGROUND: We evaluated brain tissue oxygen pressure (PO2), carbon dioxide pressure (PCO2) and pH during ischemia with brain temperature at 35 degrees and 18 degrees C in the same patient. METHODS: Surgery was performed in a 60-year-old woman to clip a large aneurysm in the left internal carotid artery (ICA). A Paratrend 7 probe measuring PO2, PCO2, and pH was inserted into tissue at risk for ischemia during ICA occlusion and brain protection was provided with 9% desflurane. One week later, hypothermic circulatory arrest with brain temperature at 18 degrees C was performed for aneurysm clipping and tissue measurements were obtained during ischemia and rewarming. RESULTS: At 35 degrees C, ICA occlusion for 16 minutes produced tissue hypoxia (PO2 = 0) and acidosis (pH = 6.70). The rate of increase of hydrogen ion (H+) reached 50 nEq.L(-1).min(-1) during ICA occlusion and there was a slow recovery of acidosis at the end of the ischemic period. During hypothermic circulatory arrest, tissue PO2 was sensitive to decreases in blood pressure and decreased rapidly during exsanguination. Although tissue pH decreased to 6.5 with 30 min of no pump flow, the rate of H+ increase during hypothermic arrest was one-third of that seen during ischemia at 35 degrees C. During rewarming from profound hypothermia, two phases of recovery from acidosis were observed, one during CO2 clearance and one after tissue reoxygenation. Recovery of acidosis occurred sooner at 18 degrees C than at 35 degrees C. CONCLUSIONS: These results show that tissue acidosis develops more slowly and recovers more rapidly with hypothermic ischemia. This may be an important mechanism of reduced ischemic injury during hypothermia.     

Long-term functional outcome following transient middle cerebral artery occlusion in the rat: Correlation between brain damage and behavioral impairment.

The assessment of both histological and functional long-term outcomes after cerebral ischemia is increasingly recommended for preclinical studies. Whereas correlations between behavioral impairments and primary ischemic lesion are documented, little is known about their relationships with remote nonischemic regions that undergo secondary degeneration, such as the thalamus. Anesthetized rats were subjected to mild (30 min) or severe (60 min) occlusion of the middle cerebral artery. Two months after ischemia, sensorimotor behavior was assessed according to the neurological score, limb-placing, adhesive-removal, and staircase tests; the final histological lesion was measured after this assessment. Cortical damage was correlated to all transient and long-lasting sensorimotor deficits, whereas striatal lesion was more consistently reflected by the forelimb-placing reflexes and adhesive-removal motor deficits. By contrast, the thalamic atrophy was not correlated to early neurological impairment, but rather to the late sensory deficit at the adhesive-removal test and to the skilled forepaw reaching alteration at the staircase test. This suggests that thalamus contributes, albeit moderately, to the ischemia-induced long-lasting sensorimotor deficits, some of which represent relevant targets for therapeutic interventions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Direct measurement of brain temperature during and after intraischemic hypothermia: correlation with behavioral, physiological, and histological endpoints

The aim of the present study was to evaluate critically the protection afforded by hypothermia against ischemic injury to the hippocampus. Hypothermic treatment was applied selectively to the brain during a 5 min carotid artery occlusion in gerbils. Following a period of recovery, two independent measures were used to assess hippocampal function: (1) an open field test of spatial memory (assessment was made during the first 10 d after ischemia) and (2) measurement of evoked potentials from area CA1 in hippocampal slices (3 weeks after the ischemic episode). The functional outcome portrayed by these tests was compared to a morphological evaluation of CA1 pyramidal cells at three rostrocaudal levels. All evaluations were carried out in the same animals. We found converging evidence that intraischemic hypothermia provides virtually complete protection against a 5 min episode of cerebral ischemia. Animals treated with hypothermia performed as well as sham-operated controls in a spatial memory task, had field potentials that were indistinguishable from normal animals and CA1 cells appeared normal when assessed histologically. In contrast, ischemia at normothermia resulted in a deficit in open field behavior (p < 0.01), diminished field potentials in stratum radiatum (p < 0.01), and near total loss of pyramidal cells in dorsal CA1 (p < 0.01). There was a remarkably high correlation between these diverse measures (r ranged from 0.7 to 0.9, p < 0.01), which provides strong support for the use of hypothermia as an effective treatment for ischemia. This study introduces a novel approach for the evaluation of putative anti-ischemic treatments: combining behavioral, electrophysiological, and histological measures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebrovascular transit characteristics of DyDTPA-BMA and GdDTPA-BMA on normal and ischemic cat brain

PURPOSE: To compare the efficacy of two nonionic T2*-shortening contrast agents, DyDTPA-BMA dysprodiamide injection and GdDTPA-BMA gadodiamide injection, as perfusion-sensitive MR imaging agents in normal and acutely ischemic brain. METHODS: The magnetic susceptibility effects of intravenous injections of 0.10-0.50 mmol/kg of each contrast agent were quantified on T2-weighted spin-echo images of cat brain before and after unilateral occlusion of the middle cerebral artery by measuring signal intensity changes in the same regions-of-interest in parietal cortex. RESULTS: In normal brain, DyDTPA-BMA produced a significantly greater loss of signal intensity than equimolar doses of GdDTPA-BMA. The magnitude of the signal intensity attenuation was dosage-dependent and proportional to the square of the magnetic moments of the two contrast agents. Restoration of baseline image signal intensity was observed within 30 min after each injection. However, injection of GdDTPA-BMA also produced a delayed, persistent hyperintensity on T2-weighted images, presumably due to its underlying T1-shortening effect. Following unilateral occlusion of the middle cerebral artery, unenhanced T2-weighted images failed to show evidence of cerebral injury for 1.5-3 hours. Administration of 0.10-1.0 mmol/kg DyDTPA-BMA shortened the time for detection of perfusion deficits (residual hyperintensity) in 22 of 36 (61%) treated cats, often to within 30 min after arterial occlusion. DyDTPA-BMA enhancement also improved lesion conspicuity in 26 of 36 (72%) cases, and disclosed very small infarcts that were not visible on T2-weighted precontrast images. Perfusion deficits in areas of partial ischemia were seen more clearly on DyDTPA-BMA-enhanced images than after equimolar injections of GdDTPA-BMA. CONCLUSIONS: Magnetic susceptibility contrast-enhanced MR imaging enables detection of perfusion deficits associated with acute cerebral ischemia well in advance of conventional T2-weighted spin-echo MR imaging without contrast. DyDTPA-BMA appears to delineate regions of ischemic damage better than GdDTPA-BMA.     

Proton and neutron excitations in superdeformed 150Tb

To determine which of two treatments for reducing ischemic injury after temporal focal ischemia is more effective, the effects of mild (33 degrees C) intraischemic hypothermia were compared with those of mannitol, the most commonly used neuroprotective agent. Four groups of Sprague-Dawley rats underwent 1 hour of endovascular middle cerebral artery occlusion followed by 23 hours of normothermic reperfusion. The four experimental groups were as follows: Group A, saline control; Group B, mannitol (25%, 1 g/kg); Group C, hypothermia; and Group D, hypothermia plus man-nitol. Laser-Doppler estimates of cortical blood flow showed that hypothermia did not affect blood flow during ischemia or reperfusion. Mannitol increased cortical blood flow during ischemia and reperfusion under both normothermic and hypothermic conditions (p < 0.05). Neurological deficit was significantly less severe in treated rats (Group B, p < 0.05; Group C or D, p < 0.01) than in controls (Group A). Infarct volume, measured on semiserial Nissl-stained sections, was significantly smaller in treated rats (p < 0.01) than in controls. Infarct volume was also significantly smaller in rats treated with hypothermia than in those treated with mannitol (Group C vs. Group B, p < 0.05); there was no difference between rats treated with mannitol and those treated with mannitol and hypothermia. All three treatments reduced infarct area in the ischemic penumbra; hypothermia with or without mannitol also reduced infarct area in the ischemic core. These results demonstrate that both mild intraischemic hypothermia and mannitol reduce infarct size and neurological deficit: hypothermia reduces infarct size more effectively than mannitol, and mannitol adds no significant protection to hypothermia, whereas hypothermia adds significant protection beyond that afforded by mannitol after brief focal ischemia followed by reperfusion in rats. The results suggest that mild intraischemic hypothermia alone, or in combination with mannitol, may be useful in avoiding ischemic injury from temporary vessel occlusion during cerebrovascular surgery.