Recovery of cognitive function after stroke

BACKGROUND AND PURPOSE: Previous studies have suggested that recovery of cognitive function after stroke is maximal within the first 3 months after onset. We performed the present study to investigate the long-term course and clinical correlates of improvement in generalized cognitive function after ischemic stroke. METHODS: We administered a battery of neuropsychological tests to 151 patients (age, 70.4 +/- 7.7 years; education, 10.4 +/- 4.6 years) at 3 months and then annually after stroke. We transformed their test results into z scores based on the performance of a stroke-free normative group, averaged those scores to create a summary score, and defined improvement in annual examinations as an increase in that summary score greater than two standard deviations above the mean first annual change of the normative group. We then used logistic regression to determine whether stroke location, syndrome, or recurrence; vascular risk factors; dementia status; depression; or demographic variables were associated with improvement. RESULTS: We found that 19 of the 151 patients exhibited improvement, which was evident only at the first annual examination in most cases. Logistic regression determined that improvement was significantly related to left hemisphere infarction relative to brain stem/cerebellar infarction (odds ratio [OR], 5.57), while the presence of a major hemispheral stroke syndrome showed a trend toward significance (OR, 3.32). Diabetes mellitus was significantly associated with a failure to exhibit improvement (OR, 0.12). Based on the logistic model, the probability of long-term improvement would be 54.0% for a patient with a left hemisphere infarct and a major hemispheral syndrome but only 11.9% if diabetes was also present. CONCLUSIONS: Long-term improvement in generalized cognitive function may be evident after stroke in association with left hemisphere infarction and severe hemispheral syndromes, while it may be compromised by diabetes, possibly because of an increased burden of cerebrovascular disease.     

Recovery in rats after spinal cord injury

Previous studies from this laboratory have shown evidence of regeneration of long descending spinal motor tracts in rats after spinal cord transection and treatment to modify the animals' immune response. In this study, less extensive surgical lesions were combined with the most favorable drug treatment (75 mg per kilogram of cyclophosphamide in a single dose) in an effort to improve the prospects for regeneration. Less than complete spinal cord transections in the rat were frequently followed by clinical and electrophysiologic evidence of return of function. Such return of function appears to depend on a reorganization of the nervous system that results in the use of the few remaining fibers to transmit motor information rather than on regeneration. Immunosuppressive treatment had no effect on these results.     

Myocardial injury after hypoxia in immature, adult and aged rats

We evaluated the abilities of isolated perfused hearts from immature (IM) (2.5-3 months), ADULT (11-13 months) and OLD (24-26 months) Fischer 344 rats to tolerate and recover from oxygen deprivation. Hearts were perfused at 60 mmHg for a 30-minute prehypoxic period with oxygenated buffer supplemented with 10 mM glucose (+insulin) and 2 mM acetate, then 30 minutes with substrate-free, hypoxic buffer gassed with 95% N2:5% CO2, and finally reoxygenated for an additional 45 minutes with the same buffer used during the prehypoxic period. During prehypoxia, all groups were similar in ventricular mechanical function, glycogen content, high-energy phosphates (HEP), reduced glutathione (GSH), Ca+2 content, and mitochondrial state 3 rates. At the end of the hypoxic period, glycogen levels were similar and almost completely depleted in all groups, HEP were lower (p < 0.05) in ADULT vs other groups, mitochondrial state 3 rates were decreased (24%, p < 0.05) only in ADULT, and GSH was depleted by 34% in IM vs only 13% in OLD (p < 0.05). After 45 minutes of reoxygenation, IM and OLD had recovered 48% and 45% of their respective prehypoxic function which was two-fold greater than the 23% recovery by ADULT. Loss of cytosolic enzymes, an indicator of sarcolemmal damage, was estimated by measuring lactate dehydrogenase (LDH) release. LDH release and Ca+2 content during reoxygenation in IM were only about half of that observed in ADULT or OLD. We conclude that immature and aged hearts tolerate and recover from hypoxia better than hearts from adults, and that the sarcolemmal membranes of immature rat hearts are less susceptible to damage from hypoxic stress than those of either older group.     

Recovery of function after neonatal ablation of the auditory cortex in rats (Rattus norvegicus)

A number of traditional Chinese medicinal herbs have become extremely interesting in the search for potential BRMs in the international medical community, especially in the United States and Japan. Naturin, a new Chinese medical herb produced by XingYa Pharmaceutical Co., Ltd., has enhanced immune response, inhibited tumor metastases and retroviral infection in animal models as well as in clinical studies. The results demonstrated that the inhibition of Natural Killer (NK) and Lymphokine-activated Killer (LAK) cell activity and lymphocyte proliferation was compromised by tumor metastases and retrovirus infection (Murine AIDS), even immunosuppression induced by surgical amputation can be restored by Naturin. It is also shown that Naturin can protect the mice from lethal total body irradiation. These studies indicated that Naturin possesses immunomodulatory effects in vivo for a broad range of stresses. The results of the clinical studies on Naturin have demonstrated: (a) significantly improved symptoms of patients, including MDS, acute and chronic leukemia, aplastic anemia, lung cancer, and association with the increased number and percentage of CD4 (Helper T-cell) which have been reduced in some patients, (b) Lymphocyte proliferation and NK cell activity which were suppressed in cancer patients can be significantly restored by Naturin treatment, (c) the addition of Naturin treatment to patients receiving radiotherapy and chemotherapy augments immune response and reduces radiation and chemotherapy injury, and (d) no cytotoxic side effects were found in patients given Naturin treatment for up to eight months.     

Contractile responses and structure of small bronchi isolated from rats after 20 months' exposure to ozone

Short-term exposure to high concentrations of ozone has been shown to increase airway responsiveness in normal humans and in all laboratory animal species studied to date. While our knowledge concerning the pulmonary effects of single exposures to ozone has increased rapidly over recent years, the effects of repeated exposures are less understood. The goal of the present study was to determine whether airway responsiveness is increased after near-lifetime exposure to ozone. Airway segments representing approximately eighth generation airways were isolated from Fischer 344 rats of both genders that had been exposed for 6 hr per day, 5 days per week for 20 months to 0, 0.12, 0.5, or 1.0 parts per million (ppm) ozone. Circumferential tension development was measured in isolated airways in response to bethanechol, acetylcholine, and electrical field stimulation. Responsiveness of the airways to the contractile stimuli was described by the effective dose or frequency that elicited half-maximum contraction (ED50) and the maximum response. Since ozone exposure is associated with remodeling of peripheral airways, smooth muscle area was determined and tension responses were normalized to the area measurements. Before normalization of tension data to smooth muscle area, neither the ED50 nor maximum response of small bronchi to the contractile stimuli was altered after chronic ozone exposure. Smooth muscle area was greater in airways isolated from animals that had been exposed to 0.5 ppm ozone. After accounting for smooth muscle area, maximum responses of the small bronchi isolated from male rats were significantly reduced after 0.12 and 0.5 ppm ozone. Although not significant statistically, a similar trend was observed in airways isolated from female rats. These results suggest that the increase in airway responsiveness associated with acute ozone exposure does not persist during near-lifetime exposure. Although the mechanism responsible for the adaptation to the effects of O3 on airway responsiveness is unknown, the results indicate that smooth muscle cell function was compromised by the chronic exposure. The mechanism(s) responsible for mediating this effect and the relevance of these results to humans remains to be determined.     

Recovery of associative function following early amygdala lesions in rats.

Adult rats with amygdala lesions made at either Postnatal Day (PND) 10 or PND40 were tested on a series of reversal tasks that tap the ability to form stimulus–reward associations. PND40 rats were significantly impaired relative to both controls and PND10 rats on learning rate of the original discrimination and subsequent reversals. Analyses of discrete learning phases revealed that the impairment was specific to the postchance phase. The PND10 group was not impaired relative to controls on any measure. These results confirm prior findings that amygdala lesions sustained in adulthood impair the formation of stimulus–reward associations. They also demonstrate that substantial sparing or recovery of function is possible when the lesion is made during early development. Furthermore, the findings support the view that behavioral recovery may be more likely if the lesion is sustained near the time of peak synaptogenesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of airway pressure-triggered and airflow-triggered ventilation in very immature infants

Failure of patient-triggered ventilation in very immature infants may be due to the use of inappropriate triggering systems. Two types of airflow trigger were therefore compared consecutively to an airway pressure (SLE) triggering system. Each comparison was made in 10 infants, < or =28 weeks of gestation. Comparison was made of the delivered volume, trigger performance and blood gases using each system for 1 h. Both comparisons showed that the airflow triggering systems performed better: one (Draeger Babylog 8000) had a higher sensitivity (p < 0.01) and the other (Bird VIP airflow trigger), in which inflation was terminated by sensing a reduction in inspiratory flow, had a lower degree of asynchrony (p < 0.01) and a tendency to deliver higher volumes. These results suggest that triggering systems sensing airflow changes may be superior to those sensing airway pressure changes in very immature infants. The use of a mechanism to synchronize the termination of inflation to the end of the patient's inspiration may offer further advantages.     

Recovery of reproductive function in rats treated with the aromatase inhibitor fadrozole

We report three cases of L-2-hydroxyglutaric acidemia and three cases of Canavan disease. The L-2-hydroxyglutaric acidemia cases are the first biochemically proven Turkish cases. Magnetic resonance imaging findings in the cases and similarities between the two diseases are emphasized. Both diseases are characterized by predominant subcortical white-matter involvement and dentate nuclei lesions with variable basal ganglia involvement. Canavan disease differs from L-2-hydroxyglutaric acidemia by the presence of typical brainstem involvement.     

Albumin exchange and polymorphonuclear vascular transit in hyperoxic pulmonary oedema in awake rats

Vascular inflammatory response to hyperoxia (FIO2 greater than 0.98) was studied in awake jugular and carotid catheterized rats. Simultaneous i.v. injection of 125I albumin (125I A), 99mTc polymorphonuclear cells (99mTc PMN) and 51Cr red blood cells (51Cr RBC) allowed to study both the macromolecule exchange through vascular endothelium and the leukocyte uptake by several organs (liver, lungs, spleen) with respect to radiolabelled red blood cells, as an intravascular reference. Rats were exposed to O2 for 24, 38 and 45 h. They were anesthetized and killed by exanguination 15 to 120 min following the tracer injection. After 45 h exposure, the plasmatic 125I A half-life decreased significantly (158 +/- 42 min for the control; 106 +/- 34 min for the exposed animals). The ratio 125I A/51Cr RBC varied significantly in the lung. The iodinated albumin exchange through lung vascular endothelium was altered at the 24th h, with a significant difference reached by the 45th h. At the same time, the pulmonary decreasing curve of 99mTc/51Cr RBC ratio versus time was not not modified. In our experimental conditions, there was no detectable variation in the lung uptake and vascular transit of PMN cells. The discussion of the results must be related with the technics used in the present work when the albumin exchange increased.     

Lung growth and airway function after lobectomy in infancy for congenital lobar emphysema

To characterize the outcome of lobectomy in infancy and the low expiratory flows which persist after lobectomy for congenital lobar emphysema, 15 subjects with this history were studied at age 8-30 yr. Total lung capacity was normal in all, but higher values (P < 0.05) were observed in nine subjects with upper lobectomy than in five subjects with right middle lobectomy. Ratio of residual volume to total lung capacity was correlated (P < 0.05) with the amount of lung missing as estimated from normal relative weights of the respective lobes. Xe(133) radiospirometry in eight subjects showed that the operated and unoperated sides had nearly equal volumes at total lung capacity, but that the operated side was larger than the unoperated side at residual volume. Perfusion was equally distributed between the two sides. Similar findings were detected radiographically in four other subjects. Forced expiratory volume in 1 s and maximal midexpiratory flow rate averaged 72 and 45% of predicted, respectively. Low values of specific airway conductance and normal density dependence of maximal flows in 12 subjects suggested that obstruction was not limited to peripheral airways. Pathologic observations at the time of surgery and morphometry of the resected lobes were not correlated with any test of pulmonary function. These data show that lung volume can be completely recovered after lobectomy for congenital lobar emphysema in infancy. The volume increase occurs on the operated side, and probably represents tissue growth rather than simple distension. The response to resection is influenced by the particular lobe resected and may be associated with decreased lung recoil near residual volume. Low expiratory flows in these subjects could be explained by several mechanisms, among which a disproportion between airway and parenchymal growth in infancy (dysanaptic growth) is most compatible with our data.     

Behavior and drug measurements in Long-Evans and Sprague-Dawley rats after ethanol-cocaine exposure

Long-Evans and Sprague-Dawley rats show differential behavioral responses to cocaethylene, a metabolite derived from the simultaneous ingestion of ethanol and cocaine. Such differences may also be manifested when these outbred strains are exposed to ethanol and cocaine. To test this hypothesis, both strains were fed an ethanol-diet (8.7% v/v) in conjunction with cocaine (15 mg/kg) injections for 15 days. The following parameters were evaluated: (a) ethanol consumption, (b) cocaine-induced behavioral activity, (c) blood ethanol levels, (d) blood, liver, or brain cocaine and cocaethylene levels, and (e) liver catalase and esterase activity. We found that Long-Evans rats drank significantly more of the ethanol diet relative to the Sprague-Dawley line during the first few days of the test session. This rat phenotype also differed significantly from the Sprague-Dawley line in terms of behavioral activity after cocaine administration. Blood ethanol levels did not differ between strains. Similarly, we failed to detect strain-dependent differences in blood, liver, or brain cocaine levels as measured by gas chromatography/mass spectrometry. Cocaethylene levels, however, were higher in blood and brain of Long-Evans relative to Sprague-Dawley cohorts. Although the ethanol-cocaine regimen produced a marked suppression of catalase and esterase activity compared with control-fed rats, this suppression was roughly equivalent in both rat phenotypes. These data are discussed in the context of genotypic background and vulnerability to polysubstance abuse.     

Ganciclovir induces reproductive hazards in male rats after short-term exposure

1. The effect of short-term treatment of ganciclovir on male reproduction in adult rats was studied. The animals were treated subcutaneously with either a single dose of 60 mg/kg daily for 5 days (Gan5day) or with 100 mg/kg administered three times at 4 h-intervals (Gan1day). The effects were investigated every 2 weeks up to 8 weeks, followed by investigations 16 and 24 weeks after treatment to detect the potential of recovery. 2. Time to mating was significantly increased in Gan1day group. The pregnancy index and outcome were only decreased 8 weeks (Gan5day and Gan1day) or 16 weeks (Gan1day) after treatment. 3. The lowest values of sperm variables studied were registered 8 weeks after treatment: The number of spermatid was reduced up to 4% (Gan5day) or 2% (Gan1day) of control; the sperm number was 5% and 8% of control in Gan5day and Gan1day, respectively. Over 80% of sperm were abnormal in Gan5day group, and only few normal sperm was detected in Gan1day group. 4. Morphological investigation of testes revealed a clearcut time-dependency effect. Four weeks after treatment distinct alterations were located exclusively in the peripheral part of the tubuli which included fat inclusions, cell and pyknotic nuclear debris and swellings of Sertoli cells. The effect was reversible 24 weeks after treatment. 5. Ganciclovir induces testicular damage and affects sperm variables after short-term exposure. The intensity and degree of the hazards varied in between the time of investigation after treatment.     

Recovery of structure and function following transection of the primary olfactory nerves in pigeons.

Studied the function of the pigeon's olfactory system before and after bilateral sectioning of the olfactory nerves. 4 adult pigeons were used in each of 3 experiments; 8 normal controls were used in Exp I. All transected nerves were found to be healed 189-302 days after sectioning. Electrical recording from the regenerated nerves revealed apparently normal receptor function and, indirectly, autonomic reflex responsiveness. Previously untrained Ss learned an olfactory discrimination after reconstitution of the peripheral olfactory system using a conditioned suppression procedure. The olfactory nerves of trained Ss were sectioned and the behavioral response recovered within 16-82 days. The gross sizes of primary olfactory nerves and olfactory bulbs were frequently much less than those of controls, but on the ultrastructural level there was no recognizable morphological deficiency in the receptor cellular organelles or terminal synaptic contacts in bulbar glomeruli. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic, episodic, reversible airway obstruction after viral bronchiolitis in rats

We have assayed a variety of 7tm chemokine receptors (CCR-2b, CCR-3, CCR-4, CCR-5, CXCR-1, CXCR-4) and two orphan 7tm receptors (V28 and EBI.1) for their ability to allow infection of CD4-negative feline kidney CCC cells by the HIV-2 strains ROD/A and ROD/B. We found that ROD/B was able to use CXCR-4 transiently expressed in CCC cells, and infection by ROD/A was enhanced 15-fold in the presence of sCD4. Feline CCC cells also became permissive to ROD/B and ROD/A entry when transiently transfected with the chemokine receptor CCR-3 or the orphan 7tm receptor V2B, when cultured in the presence of sCD4. Entry of ROD/A into CCC cells expressing CCR-3 could be blocked by 800 ng/ml eotaxin, the natural ligand for CCR-3.     

Breathing and pulmonary surfactant function in mice 24 h after ozone exposure

Systemic administration of pilocarpine, which results in status epilepticus followed by recurrent seizures in rats, is a widely used experimental model of chronic limbic epilepsy. Marked structural alterations have been documented in pilocarpine-induced epilepsy, and these include cell loss in the hippocampus and other brain areas, and sprouting of mossy and cholinergic fibers in the hippocampus. Evidence is accumulating that neurotrophins and neurotrophin receptors are involved in the cascade of these events. Two and 4 months after pilocarpine-induced epilepsy, neurons containing the 75-kDa low affinity neurotrophin receptor (p75NTR) were investigated with immunohistochemistry in the medial septal and diagonal band nuclei. No significant differences in the distribution and number of immunoreactive neurons were found in the epileptic rats compared to control saline-treated animals. However, in the epileptic animals, a significant decrease in the perikaryal size of p75NTR-immunoreactive neurons of the septal/diagonal band region was found by 60 days, and such atrophic changes were more marked in the diagonal band nuclei by 120 days. These findings indicate that the p75NTR-containing cell bodies, which include the neurons projecting to the hippocampal formation and are cholinergic in the normal brain, survive after months of spontaneous recurrent seizures, during which, therefore, a supply of p75NTR to target regions is maintained in the chronic epileptic brain. However, the present data point out that these p75NTR-containing neurons undergo a significant shrinkage in pilocarpine-induced chronic epilepsy, thus indicating that they are involved in the brain pathology of temporal lobe epilepsy.     

Recovery of delayed alternation in rats after lesions in medial frontal cortex and septum.

Two experiments using contingently reinforced T-maze alternation with 48 male Long-Evans and hooded rats found that (a) normal Ss, after achieving high accuracy in alternation with brief (0 sec) intertrial intervals (ITIs), dropped to chance levels with longer ITIs (90 sec) but reacquired effective alternation with additional practice; (b) small lesions in mediodorsal pregenual cortex had no effect on postoperative retention of alternation at either short or long ITIs; (c) however, small lesions in posterodorsal septum temporarily disrupted alternation at brief ITIs, whereas at long ITIs Ss chose randomly and never recovered; and (d) large lesions in medial frontal cortex disrupted retention of alternation at brief ITIs of 10 sec but significant recovery did occur with additional experience. Implications regarding task difficulty and locus of lesion for recovery of function are discussed. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term retention of avoidance learning by immature and adult rats as a function of environmental enrichment.

Taught 32 23-day-old female Sprague-Dawley albino rats active or passive avoidance. 32 controls received equivalent handling and shock in a different apparatus. Both groups were then exposed to an enriched or standard laboratory environment for 60 days prior to a retention test. Environmental enrichment resulted in greater forgetting of active avoidance. The lack of initial latency differences between control groups together with other indices of activity suggested that the differential forgetting was due to memorial effects rather than environmentally induced activity differences. Exp. II with 26 Ss indicated that environmental enrichment resulted in greater forgetting for both weanlings and adults, implicating extraexperimental interference as a general source of incomplete retention by the rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inducible nitric oxide synthase expression in cerebrovascular smooth muscle and neutrophils after traumatic brain injury in immature rats

The inflammatory response after traumatic brain injury (TBI) includes cytokine production, leukocyte infiltration, and microglial activation. Production of nitric oxide by inducible nitric oxide synthase (iNOS) occurs during acute inflammation outside of the CNS and in models of cerebral ischemia, and therefore may contribute to the inflammatory response after TBI. The purpose of this study was to localize and define the time course of iNOS expression after TBI in the immature rat. Immature Wistar rats (age 3.5-4.5 wk) were anesthetized and subjected to percussive trauma to the right parietal cortex. Nontraumatized rats were used as controls (n = 7). At 2, 24, 48, or 168 h (n = 3/group) posttrauma rats were killed by perfusion fixation. Brains were removed, frozen, sectioned, immunostained with antibodies against iNOS and glial fibrillary acidic protein (GFAP, a marker specific for astrocytes), and imaged using fluorescent detection systems. There was no detectable expression of iNOS in control brains. At 2h, minimal cerebrovascular iNOS expression was seen in the peritrauma area. At 24 and 48 h, there was marked peritrauma cerebrovascular iNOS expression that appeared to be restricted to vascular smooth muscle cells and infiltrated leukocytes. Further dual-immunolabeling showed that the leukocytes expressing iNOS were predominantly neutrophils. At 168 h, iNOS expression was no longer detectable. iNOS was not detectable in GFAP-positive cells. The prominent expression of iNOS protein after TBI in cerebrovascular smooth muscle cells and infiltrated neutrophils suggests that iNOS may play a role in cerebrovascular disturbances and secondary brain injury after trauma.