ISSN:0897-7151    

DOI:10.1089/neu.1994.11.1

年代:1994

数据来源: MAL

摘要:

ABSTRACTThroughout evolution the brain has acquired elegant strategies to protect itself against a variety of environmental insults. Prominent among these are signals released from injured cells that are capable of initiating a cascade of events in neurons and glia designed to prevent further damage. Recent research has identified a remarkably large number of neuroprotection factors (NPFs), whose expression is increased in response to brain injury. Examples include the neurotrophins (NGF, NT-3, NT-5, and BDNF), bFGF, IGFs, TGFs, TNFs and secreted forms of the β-amyloid precursor protein. Animal and cell culture studies have shown that NPFs can attenuate neuronal injury initiated by insults believed to be relevant to the pathophysiology of traumatic brain injury (TBI) including excitotoxins, ischemia, and free radicals. Studies of the mechanism of action of these NPFs indicate that they enhance cellular systems involved in maintenance of Ca2+homeostasis and free radical metabolism. Recent work has identified several low-molecular-weight lipophilic compounds that appear to mimic the action of NPFs by activating signal transduction cascades involving tyrosine phosphorylation. Such compounds, alone or in combination with antioxidants and calcium-stabilizing agents, have proved beneficial in animal studies of ischemic brain injury and provide opportunities for development of preventative/therapeutic approaches for TBI

ISSN:0897-7151    

DOI:10.1089/neu.1994.11.3

年代:1994

数据来源: MAL

摘要:

ABSTRACTThis two-part investigation explored the parameters and mechanisms of: (1) injury to spinal cord (SC) neurons by nonfreezing low temperatures, and (2) hypothermic protection of SC neurons subjected to a defined, physical injury (dendrite transection). Conclusions from the studies of hypothermic injury were: (1) morphologic and ultrastructural signs of stress developed in SC neurons as the temperature was decreased below 17°C; (2) most neurons showing stress during cooling died upon rewarming to 37°C; (3) spontaneous SC network activity was not significantly changed by cooling to 17°C for 2 hours and rewarming, but cooling to 10°C for 1 hour caused a reduction of burst frequency after rewarming, and cooling to 10°C for 2 hours resulted in electrical silence after rewarming; and (4) application of N-methyl-D-aspartate (NMDA) antagonists before cooling prevented neuronal death, ultra-structural damage, and loss of activity upon rewarming, but application after cooling (before rewarming) was not protective. Conclusions from the studies of hypothermic protection were: (1) cooling at 17°C for 2 hours followed by rewarming to 37°C significantly increased lesioned neuron survival, but protection was lost when the period at 17°C was increased to 6 hours; (2) NMDA blockade under normothermic (37°C) or hypothermic (17°C or 10°C for 2 hours) conditions was not more protective of lesioned neurons than cooling to 17°C (no NMDA antagonist); and (3) 200 μM thiopental or 100 μM pentobarbital increased lesioned neuron survival to a degree comparable to cooling for 2

ISSN:0897-7151    

DOI:10.1089/neu.1994.11.35

年代:1994

数据来源: MAL

摘要:

ABSTRACTChanges that occur in the localization of calcitonin gene-related peptide-like-immunoreactivity (CGRP-LI) in motoneurons, following injury to the human spinal cord, were examined. CGRP-LI above and below the level of injury was compared to normal human spinal cord. Vibratome sections were cut and processed for immunostaining using the avidin-biotin immunoperoxidase method. Whereas motoneurons above the lesion contained CGRP-LI, below the lesion the CGRP-LI was reduced. In 3 spinal cords from patients who had survived between 1 and 8 years after injury, CGRP-LI in motoneurons of lumbar spinal cord was absent or considerably diminished. In the spinal cord from one patient who had died several years after injury, there was a unilateral augmentation of CGRP immunostaining. The results suggest that CGRP levels in motoneurons are affected by spinal cord injury in humans and that CGRP levels in motoneurons may be regulated either by supraspinal afferent inputs or by muscle activity.

ISSN:0897-7151    

DOI:10.1089/neu.1994.11.63

年代:1994

数据来源: MAL

摘要:

ABSTRACTThe magnitude of behavioral deficits in traumatic brain injury (TBI) has been shown to be partly related to alterations in the balance between excitatory and inhibitory neurotransmitter release. Previous studies have demonstrated that extracellular excitatory neurotransmitter concentrations dramatically increase following experimental TBI. We examined the effects of a neuromodulatory peptide, galanin (GAL), on behavioral morbidity, as measured by sensory motor and memory performance tasks, associated with experimental TBI in the rat. A single intraventricular injection of GAL (1.0 μg,n= 8 or 10.0 μg,n= 10) or cerebrospinal fluid (CSF) vehicle (n= 10) was administered 5 minutes prior to central fluid percussion TBI in rats. Performance on sensory motor tasks was assessed prior to injury and for 5 days after TBI with beam-balance, beam-walking, and rotarod tasks. Memory performance was assessed on days 11–15 after TBI with the Morris water maze. TBI produced significant motor and memory deficits in the CSF-treated group. GAL-treated rats had significantly less magnitude of deficits compared to CSF-treated rats on beam-balance, beam-walking, and rotarod performance. The 1.0 μg GAL dose produced slightly greater protection than the 10.0 μg GAL dose. Neither GAL dose affected body weight loss or Morris water maze performance. These results suggest that the physiologic effects of GAL may reduce certain components of TBI morbidity, possibly by modulating neuronal excitab

ISSN:0897-7151    

DOI:10.1089/neu.1994.11.73

年代:1994

数据来源: MAL

摘要:

ABSTRACTWe examined the effects of (S)-emopamil, a phenylalkylamine calcium channel blocker with serotonin receptor antagonist properties, on regional cerebral blood flow (rCBF) following experimental brain injury in the rat. Animals were subjected to fluid percussion brain injury of moderate severity (2.1 atm), and received (S)-emopamil (20 mg/kg, i.p.,n= 10) or saline (n= 10) at 20 minutes postinjury and 2.5 hours after the first injection of the drug. Consecutive rCBF measurements were performed: (1) prior to injury, (2) 15 minutes, (3) 90 minutes, and (4) 4 hours postinjury, using the radiolabeled microsphere technique. Brain injury produced an acute and significant reduction of rCBF at 15 minutes postinjury in all the regions examined (p<0.05). At 90 minutes postinjury, rCF remained significantly depressed in the forebrain regions. AH brain regions showed a recovery of rCBF to normal by 4 hours following injury in saline-treated animals, with the exception of injured left parietal cortex and bilateral hippocampi, where rCBF remained significantly depressed. A significant attenuation of the trauma-induced reduction in rCBF was observed at 70 minutes after the first administration of (S)-emopamil in the forebrain regions and cerebellum (p<0.05). Following the second (S)-emopamil injection, the significant improvement in rCBF observed in left injured cortex was maintained. These results suggest that (S)-emopamil may be efficacious in reversing post-traumatic alterations in rCBF, which may contribute to the post-traumatic pathophysiologic sequelae.

ISSN:0897-7151    

DOI:10.1089/neu.1994.11.83

年代:1994

数据来源: MAL

ISSN:0897-7151    

DOI:10.1089/neu.1994.11.97

年代:1994

数据来源: MAL

ISSN:0897-7151    

DOI:10.1089/neu.1994.11.99

年代:1994

数据来源: MAL

ISSN:0897-7151    

DOI:10.1089/neu.1994.11.101

年代:1994

数据来源: MAL