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C E Hulsebosch

Publications and source records attributed to C E Hulsebosch.

At least 19 recordsLinked to original sources
PubMed2000

AIDA reduces glutamate release and attenuates mechanical allodynia after spinal cord injury.

Spinal cord injury (SCI) leads to an increase in extracellular excitatory amino acid (EAA) concentrations, resulting in glutamate receptor-mediated excitotoxicity and central sensitization. To test contributions of group I metabotropic glutamate receptors (mGluRs) in SCI induced release of glutamate and in behavioral outcomes of central sensitization following injury, we administered 1-aminoindan-1,5-dicarboxylic acid (AIDA; 0.1 nmol intraspinally), a potent group I mGluR antagonist, to rats immediately after spinal cord contusion injury. EAAs were collected by microdialysis and quantified using HPLC. AIDA significantly decreased extracellular glutamate but not aspartate concentrations and significantly attenuated the development of mechanical but not thermal allodynia. These results suggest mGluRs play an important role in injury-induced EAA release and in central sensitization following SCI.

Animals↗
PubMed2000

Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury.

Spinal cord injuries (SCI) result in a devastating loss of function and chronic central pain syndromes frequently develop in the majority of these patients. The present study uses a rodent spinal hemisection model of SCI in which mechanical and thermal allodynia develops by 24 days after injury. Post-operative paw withdrawal responses to low threshold and high threshold mechanical stimuli compared to pre-operative responses (4.78, 9.96, and 49.9 mN) were increased and were statistically significant (p<0.05) for both forelimbs and hindlimbs indicating the development of mechanical allodynia. By contrast, post-operatively, the temperature at which paw withdrawal accompanied by paw lick occurred was significantly decreased (p<0.05), indicating the development of thermal allodynia. The intrathecal application of either D-AP5, a competitive NMDA receptor antagonist, or NBQX-disodium salt, a competitive non-NMDA AMPA/kainate receptor antagonist, alleviated the mechanical allodynia and lowered the threshold of response for the high threshold mechanical stimuli in a dose-dependent manner, and these decreases were statistically significant (p<0.05). By contrast, neither the D-AP5 nor the NBQX produced a statistically significant change in the thermal allodynia behavior in either forelimbs or hindlimbs in the hemisected group. No significant changes in locomotion scores, and thus no sedation, were demonstrated by the hemisected group for the doses tested. These data support the potential efficacy of competitive excitatory amino acid receptor antagonists in the treatment of chronic central pain, particularly where input from low threshold mechanical afferents trigger the onset of the painful sensation. Furthermore, these data suggest a role for both NMDA and non-NMDA receptors in the development of plastic changes in the spinal cord that provide the underlying mechanisms for central neuropathic pain.

Animals↗
PubMed2000

Transplants of adrenal medullary chromaffin cells reduce forelimb and hindlimb allodynia in a rodent model of chronic central pain after spinal cord hemisection injury.

In the majority of patients, spinal cord injury (SCI) results in abnormal pain syndromes in which non-noxious stimuli become noxious (allodynia). To reduce allodynia, it would be desirable to implant a permanent biological pump such as adrenal medullary chromaffin cells (AM), which secrete catecholamines and opioid peptides, both antinociceptive substances, near the spinal cord. We tested this approach using a recently developed a mammalian SCI model of chronic central pain, which results in development of mechanical and thermal allodynia. Thirty day-old male Sprague-Dawley rats were spinally hemisected at T13 and allowed 4 weeks for recovery of locomotor function and development of allodynia. Nonimmunosuppressed injured animals received either control-striated muscle (n = 7) or AM (n = 10) transplants. Nociceptive behavior was tested for 4 weeks posttransplant as measured by paw withdrawals to von Frey filaments, radiant heat, and pin prick stimuli. Hemisected animals receiving AM demonstrated statistically significant reductions in both fore- and hindlimb mechanical and thermal allodynia, but not analgesia, when compared to hemisected animals receiving striated muscle transplants (P < 0.05). Tyrosine hydroxylase immunoreactivity indicated prolonged transplant survival and production of catecholamines. HPLC analysis of cerebrospinal fluid samples from animals receiving AM transplants demonstrated statistically significant increases in levels of dopamine (sevenfold), norepinephrine (twofold), and epinephrine (threefold), compared to control values several weeks following transplant (P < 0.05). By 28 days posttransplant, however, antinociceptive effects were diminished. These results support the therapeutic potential of transplanted AM in reducing chronic central pain following spinal cord injury.

Adrenal Medulla↗
PubMed2000

Alleviation of mechanical and thermal allodynia by CGRP(8-37) in a rodent model of chronic central pain.

CGRP(8-37) is a truncated version of calcitonin gene-related peptide (CGRP) that binds to the CGRP receptor with similar affinity but does not activate the receptor and is a highly selective CGRP receptor antagonist. CGRP and activation of its receptor appear to play a role in peripheral inflammatory and neuropathic models of pain although there is considerable controversy. The aim of this study was to examine possible anti-nociceptive effects of CGRP(8-37) on a model of chronic central neuropathic pain known to develop weeks after spinal hemisection. Adult male Sprague-Dawley rats were given a spinal hemisection (N=34) or a sham surgery (N=10) at the T13 spinal segment. An externally accessible PE-10 intrathecal catheter that terminated at T13 was used for drug delivery. Animals were allowed to recover for 4 weeks at which time the hemisected animals displayed mechanical and thermal allodynia bilaterally, in both forelimbs and hindlimbs. CGRP(8-37) was delivered just prior to a testing session in 1, 5, 10, or 50 nM doses in artificial cerebral spinal fluid in 10 microl volumes. CGRP(8-37) was effective in alleviating mechanical and thermal allodynia in a dose-dependent manner (P<0.05). The 50 nM dose was most efficacious for both forelimb and hindlimb responses (P<0.05). The period of efficacy was 10 min to onset for a duration of 20 min. Post-drug washout responses were not statistically significant compared to pre-drug responses. The sham control groups demonstrated no statistically significant difference at any dose of CGRP(8-37) when compared to pre-surgical baseline values. In conclusion, CGRP(8-37) is effective in abolishing mechanical and thermal allodynia produced by spinal hemisection. Consequently, the CGRP receptor may play a role in chronic central neuropathic pain and offers a novel therapeutic approach to managing chronic central pain.

Animals↗
PubMed1999

NGF levels decrease in the spinal cord and dorsal root ganglion after spinal hemisection.

To examine changes in nerve growth factor (NGF) levels in spinal cord and dorsal root ganglia (DRG) after spinal injury, male Sprague-Dawley rats weighing 150-175 g were given spinal hemisections. NGF content was measured at various post-surgical times and compared with naive controls (n = 4 per time point) in the spinal cord, DRG and blood serum by ELISA techniques (Promega). Levels of NGF in the blood serum were significantly increased 8-fold at 48h but were significantly decreased in the spinal cord and DRG by 2- to 4-fold until 7 days postsurgery (ANOVA, p < 0.05). Contrary to accepted dogma, spinal injury results in decreased levels of NGF in the spinal cord and DRG following spinal injury.

Animals↗
PubMed1998

Traumatic brain injury in rats results in increased expression of Gap-43 that correlates with behavioral recovery.

Traumatic brain injury is associated with behavioral deficits, often in the absence of histopathological or ultrastructural changes. To determine whether membrane remodeling occurs, immunocytochemical techniques were used and the density and distribution of GAP-43 were measured. GAP-43 is a membrane-bound protein, which, when phosphorylated, is thought to regulate metabolic pathways involved in membrane remodeling and neurite growth. Moderate central fluid percussion injury (FPI, 1.9-2.2 atm.) was performed on anesthetized, spontaneously hypertensive Wistar rats (SHR). Behavioral reflex recovery was consistent with moderate levels of brain injury. One, 3, 5, 7 and 9 days after injury, both sham control (n = 4) and FPI (n = 4) animals were sacrificed, the brains were removed, cryosectioned and processed. Density measurements were taken from histological sections taken at interaural 6.20 mm and bregma -2.80 mm and were found to be statistically greater (P < 0.05) than background grey matter readings in the agranular cortices, the frontal, hindlimb, parietal 1 and 2 cortices, and the hippocampus and dentate gyrus, excluding the pyramidal and granular cell layers. Density measurements taken in forelimb and hindlimb cortical regions correlate with forelimb and hindlimb recovery in foot-fault and beam balance tests (P < 0.05). We interpret these data to indicate neuronal membrane remodeling as a result of the disruption of neuronal membranes due to the impact and shearing forces associated with the FPI. The disruption and remodeling of neuronal membranes are in areas that are consistent with the loss and recovery of locomotor and spatial behavior as a result of FPI.

Animals↗
PubMed1998

A rapid and sensitive method for detecting human cells in xenogeneic hosts.

Xenografts, specifically transplantation of human cells into other species, are a valuable tool in preclinical transplantation experiments. A central issue is accurate identification of the grafted cells, particularly in cases in which cellular migration has occurred. We report that detection of grafted human cells can be achieved by in situ hybridization techniques using human centromeric probes which result in unambiguous nuclear labeling. The resulting reaction can be combined with immunocytochemical or histochemical techniques for cell-type characterization.

Animals↗
PubMed1998

Enhanced neocortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats.

BACKGROUND AND PURPOSE: D-Amphetamine administration increases behavioral recovery after various cortical lesions including cortical ablations, contusions, and focal ischemia in animals and after stroke in humans. The purpose of the present study was to test the enhanced behavioral recovery and increased expression of proteins involved in neurite growth and synaptogenesis in D-amphetamine-treated rats compared with vehicle-treated controls after a focal neocortical infarct. METHODS: Unilateral neocortical ischemia was induced in male spontaneously hypertensive Wistar rats (n=8 per time point per group) by permanently occluding the distal middle cerebral artery and ipsilateral common carotid artery in 2 groups of rats: D-amphetamine treated (2 mg/kg IP injections) and vehicle treated (saline IP injections). To determine the spatial and temporal distribution of neurite growth and/or synaptogenesis, growth-associated protein (GAP-43), a protein expressed on axonal growth cones, and synaptophysin, a calcium-binding protein found on synaptic vesicles, were examined by immunohistochemical techniques, and both density and distribution of reaction product were measured. Since the resulting infarction included a portion of the forelimb neocortex, behavioral assessments of forelimb function using the foot-fault test of Hernandez and Schallert were performed on the same rats used for immunohistochemical studies during the period of drug action and 24 hours later. A Morris water maze and other indices of behavioral assays were also measured similarly. Recovery times were 3, 7, 14, 30, and 60 days postoperatively. RESULTS: Both GAP-43 and synaptophysin proteins demonstrated statistically significant increases in density and distribution of immunoreaction product as determined by optical density measurements in the neocortex of the infarcted group treated with D-amphetamines compared with vehicle-treated infarcted controls. The GAP-43 was elevated to statistically significant levels in forelimb, hindlimb, and parietal neocortical regions ipsilateral to the infarction only at days 3, 7, and 14. By contrast, the synaptophysin demonstrated no statistically significant changes in expression at 3 or 7 days but demonstrated statistically significant increases at 14, 30, and 60 days in the forelimb, hindlimb, and parietal neocortical regions ipsilateral to the infarction as well as increased distribution in the contralateral parietal neocortex. Behavioral assessment of forelimb function indicated that improved recovery of forelimb placement on the side contralateral to the infarction was statistically significant in the D-amphetamine-treated group compared with the vehicle-treated group (P<0.025). Spatial memory, as measured with the Morris water maze, worsened in the vehicle-treated group compared with the D-amphetamine-treated group at 60 days (P<0.025). CONCLUSIONS: These data support the occurrence of neurite growth followed by synaptogenesis in the neocortex in a pattern that corresponds both spatially and temporally with behavioral recovery that is accelerated by D-amphetamine treatment. While the specific mechanisms responsible for D-amphetamine-promoted expression of proteins involved in neurite growth and synaptogenesis and of enhanced behavioral recovery are not known, it is suggested that protein upregulation occurs as a result of functional activation of pathways able to remodel in response to active behavioral performance.

Animals↗
PubMed1997

Spinal cord injury and anti-NGF treatment results in changes in CGRP density and distribution in the dorsal horn in the rat.

Spinal cord injury (SCI) results in chronic pain states in which the underlying mechanism is poorly understood. To begin to explore possible mechanisms, calcitonin gene-related peptide (CGRP), a neuropeptide confined to fine primary afferent terminals in laminae I and II in the dorsal horn of the spinal cord and implicated in pain transmission, was selected. Immunocytochemical techniques were used to examine the temporal and spatial distribution of CGRP in the spinal cord following T-13 spinal cord hemisection in adult male Sprague-Dawley rats compared to that seen in sham controls. Spinal cords from both hemisected and sham control groups (N = 5, per time point) were examined on postoperative day (POD) 3, 5, 7, 14, and 108 following surgery. Sham operated rats displayed CGRP immunoreaction product in laminae I and II outer, Lissauer's tract, dorsal roots, and motor neurons of the ventral horn. In the hemisected group, densiometric data demonstrated an increased deposition of reaction product that was statistically significant, in laminae III and IV, both ipsilateral and contralateral to the lesion that extended at least two segments rostral and caudal to the hemisection site by POD 14, and remained significantly elevated as long as POD 108. Since upregulation alone of CGRP would occur in an acute temporal window (by 2 to 3 days following spinal injury), these results are interpreted to be invasion of laminae III and IV by sprouting of CGRP containing fine primary afferents. Intrathecal delivery of antibodies against purified 2.5S nerve growth factor for 14 days to the hemisected group resulted in CGRP density in laminae I through IV that was significantly less than that seen in untreated or vehicle treated hemisected groups and to sham controls. These data indicate changes in density and distribution of CGRP following spinal hemisection that can be manipulated by changes in endogenous levels of NGF. These observations suggest possible strategies for intervention in the development of various pain states in human SCI.

Afferent Pathways↗
PubMed1997

Transplant therapy: recovery of function after spinal cord injury.

Spinal cord injuries (SCI) result in devastating loss of function and altered sensation. Presently, victims of SCI have few remedies for the loss of motor function and the altered sensation often experienced subsequent to the injury. A goal in SCI research is to improve function in both acute and chronic injuries. Among the most successful interventions is the utilization of transplanted tissues toward improved recovery. The theory is that the transplanted tissue could (1) bridge the spinal lesion and provide chemical and/or mechanical guidance for host neurons to grow across the lesion, (2) bridge the spinal lesion and provide additional cellular elements to repair the damaged circuitry, (3) provide factors that would rescue neurons that would otherwise die and/or modulate neural circuits to improve function. A variety of tissues and cells have been added to the adult mammalian spinal cord to encourage restoration of function. These include Schwann cells, motor neurons, dorsal root ganglia, adrenal tissue, hybridomas, peripheral nerves, and fetal spinal cord (FSC) tissue en bloc or as disassociated cells. It is postulated that these tissues would rescue or replace injured adult neurons, which would then integrate or promote the regeneration of the spinal cord circuitry and restore function. In some instances, host-appropriate circuitry is supplied by the transplant and functional improvement is demonstrated. In this presentation, specific examples of recent work with transplanted tissue and cells that demonstrate improved behavioral outcome are presented. New recent work describing the in vitro propagation and characterization of human fetal spinal cord multipotential progenitor cells are also described in the context of a potential resource for transplantable cells. Additionally, data from transplantation experiments of human FSC cells into nonimmunosuppressed rat spinal cord are described, and the resultant improvements in behavioral outcome reported. Lastly, directions for future SCI research are proposed.

Animals↗
PubMed1997

Chronic central pain after spinal cord injury.

Spinal cord injury (SCI) frequently results in dysesthesias that have remained refractory to clinical treatments despite a variety of interventions. The failure of therapeutic strategies to treat dysesthesias after SCI is due to the lack of attention given to mechanisms that elicit chronic pain following SCI. An overview of the literature with respect to the development of chronic pain in the SCI patient population will be given. In addition, a mammalian model of chronic central pain following spinal cord trauma will be presented. The model is characterized by the development of mechanical and thermal allodynia, as demonstrated by measuring the thresholds of accepted nociceptive tests, the paw withdrawal responses accompanied by changes in behavior consistent with the experience of noxious stimuli. In addition, vocalization responses that are accompanied by postural and behavioral changes consistent with the receipt of a noxious stimulus and involving supraspinal pathways are measured. Locomotor function was also tested and scored using the Basso, Beattie, and Bresnahan (BBB) open field test scale. Our data indicate that somatosensory thresholds for both mechanical and thermal stimuli that elicit paw withdrawal (flexor reflex) or vocalizations, accompanied by complex changes in behavior, are significantly different following SCI. These changes represent the development of mechanical and thermal allodynia. To determine the underlying mechanism for the altered sensory responses, we used electrophysiological techniques to determine if nociceptive dorsal horn neurons demonstrated increased excitability to peripheral stimulation as evidenced by increased responses to natural somatosensory stimuli. The data presented support the development of central sensitization of dorsal horn neurons after spinal cord hemisection. This provides a mechanism for the development of mechanical and thermal allodynia after SCI. Hypotheses that account for the development of the central pain state after SCI, as well as therapeutic interventions to ameliorate the pain state, are discussed.

Animals↗
PubMed1995

NGF-producing transfected 3T3 cells: behavioral and histological assessment of transplants in nigral lesioned rats.

The rodent fibroblast clonal cell line, 3T3, was retrovirally transfected with the rat nerve growth factor (NGF) gene and selected for NGF synthesis. This study tested the hypothesis that transplanted 3T3 cells, transfected to secrete nerve growth factor (3T3NGF+), change motor behavioral indices created by striatal denervation in a dose-dependent fashion. 3T3NGF+ cells were transplanted into the lateral ventricle of rats following ipsilateral lesions of the substantia nigra pars compacta by stereotaxic injections of 6-hydroxydopamine (10 micrograms), an established lesion model. Control groups included vehicle injections and transplanted untransfected cells. The extent of the lesions was measured by determining rotational behavior before and two weeks after transplantation. Immediately prior to transplantation, cells were incubated with the fluorescent dye marker, Dil. To assess cell viability, whole brains were cryosectioned and examined for Dil-labeled 3T3 cells using fluorescent microscopy. The number of Dil-labeled profiles in five animals per group were counted in at least five noncontiguous sections per animal. From these data a statistically derived estimate of viable, transplanted 3T3 cells was obtained. The number of surviving transplanted cells correlated with the behavioral changes measured. The 3T3NGF+ transplants reduced rotational behavior, while control 3T3 transplants exacerbated rotational behavior. Thus, while NGF delivery was found to be beneficial, it was apparent that naive 3T3 had detrimental effects. These results underscore the importance of making dose-response measurements when attempting transplant-based modifications of CNS behavior.

3T3 Cells↗
PubMed1995

Neocortical neural sprouting, synaptogenesis, and behavioral recovery after neocortical infarction in rats.

BACKGROUND AND PURPOSE: Neuroanatomical plasticity is well described in lesions of the hippocampus but remains a subject of some controversy in the neocortex. The purpose of the present study was to measure the neocortical distribution and density of expression of proteins known to be involved in neurite growth or synaptogenesis and to correlate the neocortical expression with behavioral recovery after a focal neocortical infarction. Focal neocortical infarction creates a circumscribed lesion in the neocortex that provides a denervation stimulus for neurite growth and synaptogenesis. METHODS: Unilateral neocortical ischemia was induced in male spontaneously hypertensive Wistar rats (n = 4 per time point) by permanent occlusion of the distal middle cerebral artery and ipsilateral common carotid artery. To determine the spatial and temporal distribution of neurite growth and/or synaptogenesis, GAP-43, a growth-associated protein expressed on axonal growth cones, and synaptophysin, a calcium-binding protein found on synaptic vesicles, were examined by immunohistochemical techniques. The reaction product was measured, and the distribution was recorded. Since the resulting infarction included a portion of the forelimb neocortex, behavioral assessments of forelimb function that used the foot-fault test of Hernandez and Schallert were performed on the same rats used for immunohistochemical studies. Recovery times were 3, 7, 14, 30, and 60 days after surgery. RESULTS: Both GAP-43 and synaptophysin proteins demonstrated statistically significant increases in the density of immunoreaction product as determined by optical density measurements in the neocortex of infarcted rats compared with sham controls. The GAP-43 was elevated to statistically significant levels in forelimb, hindlimb, and parietal neocortical regions medial and lateral to the infarction only at days 3, 7, and 14. In contrast, synaptophysin demonstrated no statistically significant changes in expression at 3 or 7 days but demonstrated statistically significant increases at 14, 30, and 60 days in the forelimb, hindlimb, and parietal neocortical regions medial and lateral to the infarction as well as in the contralateral parietal neocortex. Behavioral assessment of forelimb function indicated impairment of forelimb placement on the side contralateral to the infarction that trended toward control values at 14 days and was not significantly different from controls by 30 days. CONCLUSIONS: These data support the occurrence of neurite growth followed by synaptogenesis in the neocortex, ipsilateral and contralateral to neocortical ischemia, in a pattern that corresponds both spatially and temporally with behavioral recovery. Thus, neuroanatomical remodeling in the neocortex provides a mechanism for recovery of function.

Animals↗
PubMed1993

Acute increase in expression of growth associated protein GAP-43 following cortical ischemia in rat.

Focal cerebral ischemia creates an area of infarction that is surrounded by neuronal tissue that may respond to nearby damage by creating neurite growth. To determine if axonal sprouting occurs after infarction, antibodies to growth associated protein MW 43,000 (GAP-43), a protein expressed on axonal growth cones, were used to assess the level of GAP-43 immunoreactivity as a measure of sprouting. Cerebral ischemia was induced in spontaneously hypertensive rats by permanently occluding the distal middle cerebral artery and ipsilateral common carotid artery. After 1 week of recovery, the animals were perfused, the brains removed, processed, and optical densities of the immunoreaction were measured. The cortex surrounding the infarcted area had increased optical densities (mean +/- S.D. = 14.2% +/- 5.5) compared to the optical density values measured in similar areas in the contralateral hemisphere (mean +/- S.D. = 6.0% +/- 3.3), a 136% increase that is statistically significant, P < 0.05 Student's t-test. We hypothesize that this increase in GAP-43 reaction product is due to axonal sprouting in the cortex surrounding an area of infarction. These data, coupled with previous work examining synaptophysin levels after cortical infarction, support the hypothesis of sprouting and synaptogenesis in the cortex following cerebral infarction.

Animals↗
PubMed1993

Plasma nerve growth factor access to the postnatal central nervous system.

The accessibility of macromolecules to the postnatal mammalian central nervous system is a subject of controversy and importance. One of the biologically important macromolecules in neural development, nerve growth factor (NGF), is thought to be unable to cross the blood-brain barrier in postnatal mammals. In this study, I125 labeled 7S NGF was systemically administered to postnatal rats and was found to accumulate in the brain in significant levels. In addition, brains from saline perfused rats contained intact 7S NGF as determined by gel autoradiography. Radiolabeled NGF was found to be localized to specific areas corresponding to p75 NGF receptor distribution in the hippocampus and cortex by autoradiography. Circulating plasma NGF has access to the developing postnatal neuraxis where it may exert a humoral trophic function.

Animals↗
PubMed1993

Migration and differentiation of PC12 cells transplanted into the rat spinal cord.

To test the hypothesis that transplanted neuronal or neuronal-like cell lines, grown in vitro, might survive and differentiate in the mammalian spinal grey matter, adult male Sprague-Dawley rats (N = 5) were injected with a suspension of between 3 x 10(5) and 1.0 x 10(6) DiI labeled, undifferentiated rat pheochromocytoma (PC12) cells in sterile phosphate buffered saline. The PC12 cell line was chosen since, in certain in vitro conditions, this cell line serves as a model of neuronal differentiation, which includes the ability to conduct action potentials and form functional synapses. After a survival time of 7 or 8 days, the spinal cords were removed, cryosectioned longitudinally and examined for detection of DiI labeled PC12 cells using fluorescent microscopy. The number of DiI labeled profiles and the proportions of the DiI cells which were differentiated were counted per section in at least five non-contiguous sections per animal. Differentiation was defined as cells with neurite-like extension which exceeded twice the soma diameter. Results demonstrated the following: (1) from 2 to 15% of the transplanted PC12 cells survived; (2) migration within the spinal grey matter occurred since PC12 cells were found as much as 510 microns away from the injection site; (3) of the surviving PC12 cell population, a proportion of between 60 and 80% were differentiated, many with two or more neurite-like processes, in all of the rats; (4) no mitotic profiles were observed in DiI labelled cells; (5) undifferentiated PC12 cells were juxtaposed to the lumens of small blood vessels or within the lesion cavity. Although the specific factors remain to be elucidated, the observed PC12 migration and differentiation within the host spinal grey matter appears to be controlled by factors in the microenvironment. These data support the use of a homogeneous in vitro population of neuronal or neuronal-like cells, which are readily accessible to transfection with the appropriate genes, as transplant sources for the injured spinal cord.

Action Potentials↗
PubMed1992

Increase in synaptophysin immunoreactivity following cortical infarction.

Plasticity in the central nervous system has been demonstrated using lesions of the hippocampus and rhinal cortex but has not been well studied after cerebral ischemia. Focal cerebral ischemia creates an area of infarction that is surrounded by neuronal tissue that may respond to nearby damage by creating new synapses. To determine if synaptogenesis occurs, antibodies to synaptophysin, a calcium-binding protein found on synaptic vesicles, were used with immunohistochemical techniques to assess the level of synaptophysin immunoreactivity as a measure of changes in the number of synapses. Cerebral ischemia was induced in hypertensive rats by permanently occluding the distal middle cerebral artery and ipsilateral common carotid artery. After 2 months recovery, the animals were perfused and the brains removed for immunohistochemical processing and evaluation. When comparing the cortex surrounding the infarcted area to similar areas on the contralateral side of the brain, the infarcted side had increased levels of anti-synaptophysin like activity that are statistically significant. We hypothesize that this increase in synaptophysin immunoreactivity is due to an increase in synapses in the cortex surrounding an area of infarction and supports the hypothesis of plasticity in the cortex following cerebral infarction.

Animals↗