Role of group I metabotropic glutamate receptors in traumatic spinal cord white matter injury

Metabotropic glutamate receptors (mGluRs) participate in glutamate neural transmission, but their role in the pathophysiology of spinal cord injury (SCI) has not been explored. Accordingly, we examined the role of group I mGluRs, which are linked to phospholipase C, in mediating SCI using an in vitro model. A dorsal column segment was isolated from the spinal cord of adult rats, maintained in vitro, and injured by compression for 15 sec with a clip having a 2 g closing force. Under control conditions after SCI, the compound action potential (CAP) amplitude was reduced to 69.1 +/- 5.4% of baseline. Blockade of group I mGluR receptors with MCPG, 4CPG, or AIDA resulted in improved recovery of CAP amplitude (82.2 +/- 2.0%, 86.2 +/- 3.9%, and 86.0 +/- 2.5% of baseline, respectively). The group I/II agonist trans-ACPD and selective group I agonist DHPG exacerbated the posttraumatic reduction of CAP amplitude. The phospholipase C inhibitor U-73122 improved recovery of CAP amplitude after traumatic spinal cord axonal injury. Western blotting and immunocytochemistry demonstrated the presence of mGluR1alpha-immunopositive astrocytes and the absence of mGluR5 in spinal cord white matter. These studies are consistent with the hypothesis that activation of group I mGluR receptors after SCI exacerbates posttraumatic axonal injury through a phospholipase C dependent mechanism. The presence of mGluR1alpha labeling on astrocytes suggests a role for these cells in the pathophysiology of SCI. Additional studies in vivo, are required to further clarify the role of mGluRs in acute traumatic SCI.     

Predicting neurologic recovery in traumatic cervical spinal cord injury

OBJECTIVE: Traumatic spinal cord injury (SCI) affects 8,000 to 10,000 individuals per year in the United States. One of the most difficult tasks confronting the clinician is the discussion of neurologic recovery and prognosis with the patient and/or family. Our objective is to provide a guide for practitioners to accurately predict neurologic outcome in acute traumatic cervical SCI (tetraplegia). DATA SOURCE: Published reports obtained through MEDLINE search, texts, and studies presented at national conferences. STUDY SELECTION: Peer reviewed studies, in English language, that discussed prognosis after traumatic SCI. CONCLUSION: A comprehensive physical examination of the acute SCI patient is essential in determining the initial level and classification of the injury and is the most accurate method to predict neurologic recovery. Other diagnostic tests, including somatosensory evoked potentials, magnetic resonance imaging, and transcranial magnetic stimulation, may be helpful in further determining outcome when used in association with the clinical examination. The understanding of neurologic recovery should help predict ultimate functional capability and potential needs.     

The skeleton after spinal cord injury. Part 1. Theoretical aspects

Sublesional osteoporosis occurs after acute spinal cord injury (SCI), preferentially weakening the skeleton below the level of the neurological lesion. Although its pathogenesis is unclear, it resembles post-menopausal, high turnover osteoporosis. Physical and pharmacologic therapies are currently being tested for their ability to prevent early loss and restore lost bone. Although treatment strategies hold promise, preservation of skeletal strength after injury may ultimately rest on lifestyle decisions made early in life. If skeletal strength is to be maintained after SCI, ways must be found to optimize skeletal strength prior to injury, arrest early losses, and stabilize, if not restore, lost bone over time.     

Brain-derived neurotrophic factor stimulates hindlimb stepping and sprouting of cholinergic fibers after spinal cord injury

Neurotrophic factors have been proposed as a therapeutic treatment for traumatic brain and spinal cord injury. The present study determined whether exogenous administration of one such factor, brain-derived neurotrophic factor (BDNF), could effect behavioral recovery and/or histopathological changes after spinal cord injury. Adult rats received a mild or moderate contusion injury or complete transection of the mid-thoracic spinal cord. Immediately thereafter, they were infused intrathecally with vehicle or BDNF for 28 days. Behavioral recovery was evaluated for 6 weeks after injury, at which time the rats were sacrificed and the spinal cord tissue was examined histologically. The infusion of BDNF resulted in acute stimulation of hindlimb activity. These effects included activation of alternating airstepping in injured rats when the hindlimbs were unloaded as well as slight improvements in the rate of recovery in open field locomotion score. BDNF infusion was also associated with enhanced growth of cholinergic fibers at the injury epicenter, but did not affect white matter sparing or density of serotonergic axons at or below the injury site. Based on immunohistochemical detection of BDNF protein distribution, these described effects are likely to be mediated by the activation of cells and axons within the central injury region and the along the peripheral rim of the spinal cord. Together, these findings demonstrate that the exogenous infusion of BDNF after spinal trauma can influence postinjury outcome through mechanisms that include acute stimulation of hindlimb activity and neuritogenesis at the injury site.     

Non-operative treatment of comminuted fractures of the proximal humerus in elderly patients

The aim of this paper is to review the incidence and characteristics found in traumatic spinal cord injury (SCI) occurring in patients with long-standing ankylosing spondylitis (AS). The incidence of patients with traumatic SCI admitted to our unit from January 1984 to February 1996 was 2% (15 out of 893). They were all men with a mean age of 56 years. Most frequently the etiology of the lesion was a motor vehicle accident and the injury was mainly due to a hyperextension mechanism. Acute spinal fracture occurred in 13 patients, all involving the cervical region. No fracture was observed in two patients with thoracic neurological level. Three patients presented with an interval free period of neurological symptoms in whom a spinal epidural hematoma was visualized with magnetic resonance imaging. On admission eight patients were diagnosed as having complete SCI and the other seven an incomplete SCI. In the acute phase, respiratory complications were most frequent, causing six patients to die. Treatment was conservative in 14 patients. Multidisciplinary management of these patients should be implemented in an institution equipped with both a Spinal Injury Unit and an Intensive Care Unit.     

Defining assessment parameters in dual injuries: spinal cord injury and traumatic brain injury

Assessment parameters for muscle testing in the individual with a spinal cord injury (SCI) have been clearly defined by the American Spinal Injury Association (ASIA). However, the ASIA standard requires the individual's participation in reporting sensory information and he/she must be able to perform specific tasks to complete the examination. In an individual with a dual injury, a SCI and a traumatic brain injury (TBI), neurological assessment can be impeded by the individual's inability to participate in the exam. Assessment needs to incorporate both cognitive and physical parameters that will appropriately assess both injuries. This article reviews the assessment parameters for both spinal cord injury and traumatic brain injury and provides assessment guidelines for bedside evaluation of functional ability. In addition, a review of the biomechanics of injury will provide a model for understanding dual injury.     

Alteration of thromboxane A2/prostacyclin and their effect on spinal cord blood flow in experimental spinal cord injury in rats

In order to document the contribution of Thromboxane (TXA2) and Prostacyclin (PGI2) to the secondary damage following spinal cord injury (SCI) and their effects on spinal cord blood flow (SCBF), the alteration of SCBF, TXB2 and 6-keto-PGF1 alpha concentration in injury site (T13-L1) and adjacent cords (upper: T12, under: L2) were studied using a rat SCI model induced by Allen's weight drop method (50g-cm). The result showed that after SCI the SCBF in injury site significantly reduced during 1-2 hrs and reduced further during 4-8 hrs. The SCBF in adjacent cords also decreased during 4-8 hrs. TXB2 levels significantly increased at 1 hr and reached peak value at 4 hrs. The 6-keto-PGF1 alpha concentration also significantly increased at 1 hr and maintained that level for 24 hrs. The TXB2/6-keto-PGF1 alpha ratio was significantly elevated at 1 hr and reached its peak at 4 hrs after SCI, then gradually decreased to the preinjury level during 8-24 hrs. The negative correlation of SCBF with TXB2 concentration and TXB2/6-keto-PGF1 alpha ratio were appeared. The experimental results indicated that the imbalance of TXB2/6-keto-PGF1 alpha could be the main cause of microcirculatory disturbance and secondary damage in SCI.     

Effect of carotenoids on the respiratory burst of rat peritoneal macrophages

Numerous factors are involved in the spread of secondary damage in spinal cord after traumatic injury, including ischemia, edema, increased excitatory amino acids, and oxidative damage to the tissue from reactive oxygen species. Neutrophils and macrophages can produce reactive oxygen species when activated and thus may contribute to the lipid peroxidation that is known to occur after spinal cord injury. This study examined the rostral-caudal distribution of neutrophils and macrophages/microglia at 4, 6, 24, and 48 h after contusion injury to the T10 spinal cord of rat (10 g weight, 50 mm drop). Neutrophils were located predominantly in necrotic regions, with a time course that peaked at 24 h as measured with assays of myeloperoxidase activity (MPO). The sharpest peak of MPO activity was localized between 4 mm rostral and caudal to the injury. Macrophages/microglia were visualized with antibodies against ED1 and OX-42. Numerous cells with a phagocytic morphology were present by 24 h, with a higher number by 48 h. These cells were predominantly located within the gray matter and dorsal funiculus white matter. The number of cells gradually declined through 6 mm rostral and caudal to the lesion. OX-42 staining also revealed reactive microglia with blunt processes, particularly at levels distant to the lesion. The number of macrophages/microglia was significantly correlated with the amount of tissue damage at each level. Treatments to decrease the inflammatory response are likely to be beneficial to recovery of function after traumatic spinal cord injury.     

Vocational interests of middle-aged men with traumatic spinal cord injury.

Objectives: Describe vocational interests of middle-aged men with traumatic spinal cord injury (SCI). Participants: Seventy-nine Caucasian men with traumatic SCI (mean age?=?44 years; mean time since onset?=?20 years), 74% with quadriplegia. Measure: Strong Interest Inventory. Results: Replicated the unique pattern of interests found by D. E. Rohe and G. T. Athelstan (1982) among younger men with SCI. Compared with the normative sample, participants were more introverted, less academically oriented, and primarily interested in physically challenging and action-oriented occupations despite their functional limitations. Conclusions: Middle-aged men with traumatic SCI have the same unique vocational interest pattern as their younger peers. This pattern is not an artifact of age or time since onset and may partially explain low rates of employment after SCI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Apoptosis after traumatic human spinal cord injury

OBJECT: Apoptosis is a form of programmed cell death seen in a variety of developmental and disease states, including traumatic injuries. The main objective of this study was to determine whether apoptosis is observed after human spinal cord injury (SCI). The spatial and temporal expression of apoptotic cells as well as the nature of the cells involved in programmed cell death were also investigated. METHODS: The authors examined the spinal cords of 15 patients who died between 3 hours and 2 months after a traumatic SCI. Apoptotic cells were found at the edges of the lesion epicenter and in the adjacent white matter, particularly in the ascending tracts, by using histological (cresyl violet, hematoxylin and eosin) and nuclear staining (Hoechst 33342). The presence of apoptotic cells was supported by staining with the terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling technique and confirmed by immunostaining for the processed form of caspase-3 (CPP-32), a member of the interleukin-1beta-converting enzyme/Caenorhabditis elegans D 3 (ICE/CED-3) family of proteases that plays an essential role in programmed cell death. Apoptosis in this series of human SCIs was a prominent pathological finding in 14 of the 15 spinal cords examined when compared with five uninjured control spinal cords. To determine the type of cells undergoing apoptosis, the authors immunostained specimens with a variety of antibodies, including glial fibrillary acidic protein, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), and CD45/68. Oligodendrocytes stained with CNPase and a number of apoptotic nuclei colocalized with positive staining for this antibody. CONCLUSIONS: These results support the hypothesis that apoptosis occurs in human SCIs and is accompanied by the activation of caspase-3 of the cysteine protease family. This mechanism of cell death contributes to the secondary injury processes seen after human SCI and may have important clinical implications for the further development of protease inhibitors to prevent programmed cell death.     

Biology of neurological recovery and functional restoration after spinal cord injury

OBJECTIVE: This article reviews the anatomic and pathophysiological bases for recovery of neurological function after experimental or clinical spinal cord injury (SCI). METHODS: Current knowledge regarding the recovery of neurological function after experimental or clinical SCI was reviewed to determine the biological basis of neurological recovery. RESULTS: There is a great propensity for recovery after clinical or experimental SCI. An examination of the anatomic basis of recovery indicates that there is a potential for both root and cord recovery, with the latter involving recovery of both gray and white matter of the cord. Resolution of acute injury events, such as hemorrhaging, and resolution of secondary pathophysiological processes, such as ischemia and excitotoxicity, can each account for recovery. The third recovery mechanism involves regrowth or regeneration of nervous tissue, resulting from either inherent or induced processes. CONCLUSION: During the Decade of the Brain, there has been a profusion of very promising in vitro and in vivo studies that have shown enhanced neurological recovery after experimental or clinical SCI.     

Pregnancy in women with spinal cord injuries

Most women with spinal cord injuries (SCI) resume normal reproductive function, can have sexual relationships, and become pregnant. Pregnancy is not contraindicated in women with SCI, but pregnant women with acute or chronic SCI pose unique challenges for perinatal health care providers. The normal physiologic changes of pregnancy may predispose women with SCI to potentially life-threatening complications, including autonomic hyperreflexia, pyelonephritis, respiratory insufficiency, thrombophlebitis, and unattended delivery of the infant. This article reviews the effect of SCI on female reproduction, pregnancy, and labor, and summarizes the treatment of the pregnant woman with a spinal cord injury.     

Neuropsychological impairments after spinal cord injury: A comparative study with mild traumatic brain injury.

Objective: To determine if individuals with mild traumatic brain injury (MTBI) perform differently on neuropsychological measures than individuals with spinal cord injury (SCI) having no loss of consciousness. Design and Participants: Data were collected prospectively on 33 matched pairs of individuals with SCI or MTBI. Independent t tests were performed to identify differences between the SCI and MTBI groups. Results: Although those with SCI generally outperformed individuals with MTBI, no meaningful between-groups differences were noted on 5 of the 10 neuropsychological tests administered. Greater than 40% of the SCI patients were identified as having impairments in processing speed, motor speed, and verbal learning. Conclusions: Treatment planning after SCI should include procedures to identify cognitive deficits that may complicate adjustment to disability and delay acquisition of new skills. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Apoptosis as a mechanism of neuronal cell death following acute experimental spinal cord injury

The complex biochemical interactions following acute spinal cord injury have undergone considerable investigation recently. Progress has been made in discovering both primary and secondary injury cascades that combine to produce the ultimate neurologic insult. Traditionally, neuronal and supporting cell death following spinal cord injury have focused on necrotic death pathways resulting passively from the actual mechanical tissue damage and inflammatory processes which follow. However, the occurrence of programmed apoptotic cell death which is an actively mediated cellular process may occur following acute spinal cord injury and, if present, may play a role in the ultimate neurologic insult. In this study, we document a chronologically-specific course of apoptotic cell death by the TUNEL assay technique following an acute experimental spinal cord injury in the rat model. In this manner, apoptotic cell death following acute spinal cord injury may play a pivotal role in the secondary injury cascade which produces the ultimate neurologic insult and may allow potential for mediating neuronal survival via anti-apoptotic factors such as the protooncogene Bcl-2.