摘要:

ABSTRACTA new experimental model of mechanical brain injury was produced in the laboratory ferret(Mustela putorius furo)using a stroke-constrained pneumatic impactor. Cortical impacts were made on vertex to the intact dura mater overlying the cerebral cortex with contact velocities ranging from 2.0 to 4.0 m/sec and with deformations of 2.0 to 5.0 mm. The dwell time of the impact and the stability of the skull during impact were verified with high speed (1000 to 3000 frames/sec) cineradiography. Systemic arterial blood pressure, heart rate, and respiration were monitored, and postinjury changes were recorded. Anatomic brain injury, including subdural hematoma, subarachnoid hemorrhage, tears or rents of the dura mater, and contusions of the cortex, brainstem, cervical spinal cord, and cerebellum was observed. Injury responses ranged from no apparent anatomic injury or alterations in the systemic physiology at low severity impact (2.0 m/sec, 2.0 mm) to immediate fatality in the highest severity impact groups (4.0 m/sec, 4.0 mm). The range of changes in systemic physiology and of pathology in the brain, brainstem, and spinal cord was a function of both contact velocity and the amount of brain deformation. In two cases where postinjury time was 8–10 h, diffuse axonal injury, indicated by beaded axons and retraction balls, was present in subcortical regions underlying the site of impact. The spectrum of anatomic injury and systemic physiologic responses closely resembled aspects of closed head injury seen clinically. This procedure complements and improves on existing techniques by allowing independent control of contact velocity and level of deformation of the brain to facilitate biomechanical and analytic modeling of brain trauma. Graded cortical contusions and subcortical injury are produced by precisely controlled brain deformations, thereby allowing questions to be addressed regarding the influence of contact velocity and level of deformation on the anatomic and functional severity of brain injur

ISSN:0897-7151    

DOI:10.1089/neu.1988.5.1

年代:1988

数据来源: MAL

摘要:

ABSTRACTThe biochemical mechanisms mediating delayed or secondary tissue injury after central nervous system trauma remain speculative. We have demonstrated previously that traumatic brain injury in rats causes a rapid decline in tissue intracellular free magnesium [Mg]fand total magnesium [Mg]tconcentrations, which were significantly correlated with injury severity. In order to examine the relationship between magnesium and traumatic brain injury, we assessed whether (1) magnesium deficiency exacerbates or (2) magnesium treatment improves posttraumatic outcome following fluid–percussion brain injury (2.0–2.4 atm) in rats. Animals placed on magnesium-deficient diet for 14 days showed a 15% decrease in brain [Mg]fas measured by phosphorus (31P) magnetic resonance spectroscopy (MRS). Magnesium deficiency significantly exacerbated neurologic dysfunction and increased mortality following injury when compared to normally fed saline-treated controls. Conversely, pretreatment with magnesium sulfate (0.1 mEq) 15 min before brain injury prevented the fall in [Mg]fobserved by31P MRS in saline-treated animals and significantly improved both cellular bioenergetic state and chronic posttraumatic neurologic outcome. These combined observations suggest that alterations in brain [Mg]fafter trauma may play a role in the pathophysiology of traumatic brain inj

ISSN:0897-7151    

DOI:10.1089/neu.1988.5.17

年代:1988

数据来源: MAL

摘要:

ABSTRACTAntagonism of N-methyl-d-aspartate (NMDA) excitatory amino acid receptors limits tissue damage after experimental cerebral ischemia. Spinal cord trauma leads to a progressive decline in blood flow that is associated with secondary tissue damage. In the present studies, we evaluated the hypothesis that NMDA receptor activation contributes to the pathophysiology of spinal cord injury by examining the effects of the NMDA antagonist MK801 after impact trauma to rat thoracic spinal cords. MK801, in doses of 1.0 and 5.0 mg/kg administered intravenously (IV) at 15 min after trauma, improved long-term neurologic recovery. At a dose of 1.0 mg/kg, the drug reduced histologic changes as well as alterations in certain tissue cations found after spinal trauma. These findings suggest that excitotoxins contribute to the pathophysiology of spinal cord injury and that early treatment with NMDA antagonists may reduce posttraumatic tissue damage.

ISSN:0897-7151    

DOI:10.1089/neu.1988.5.33

年代:1988

数据来源: MAL

摘要:

ABSTRACTReactive axonal changes following fluid-percussion brain injury were studied in the highly organized afferent pathways of the cat visual system. The visual system offers several features advantageous to the study of traumatic brain injury. Specifically, as the retinal cells of origin of the optic nerve and tract are isolated from the employed fluid-percussion injury, concomitant traumatically induced somatic change is not a confounding variable. Additionally, the existence of axons of varying diameters and topographic localization within the visual pathways allows the relationship between both fiber size and distribution and their predilection for traumatically induced change to be considered. Since the visual pathway is a highly organized sensory pathway, data obtained in this system can be compared with similar studies previously conducted in motor systems. In these experiments, 20 adult cats were subjected to brain injury and killed at posttraumatic survival periods ranging from 2 to 60 days. Six cats received intravitreous injections of horseradish peroxidase (HRP) to aid in the recognition of axonal change. At the designated survival time, all animals were perfused with aldehydes. The visual system from optic chiasm to lateral geniculate was sectioned and prepared for routine light (LM) and electron microscopic (TEM) study. Animals injected with HRP were processed for the LM and TEM visualization of HRP reaction products. By the second posttraumatic day, reactive axonal swellings were observed in the optic tracts as they entered the medial intralaminar nuclei of the lateral geniculate bodies. Proximal segments of the reactive axons showed enlargement and lobulation, whereas the distal segments underwent wallerian degeneration. Over a 2 week posttraumatic course, some axonal swellings persisted unchanged, some degenerated, and others initiated regenerative sprouting. With continued survival, however, all the reactive swellings manifested only progressive degenerative change. These reactive axonal changes appeared to constitute a primary response to the traumatic episode and occurred without concomitant damage to either the related brain parenchyma or its intrinsic vasculature. Although these findings replicate many of those previously described in motor pathways, new conceptual information has been provided. These studies preclude concomitant somal damage as a confounding variable and suggest that large-caliber axons are susceptible to the shear and tensile forces of traumatic brain injury.

ISSN:0897-7151    

DOI:10.1089/neu.1988.5.47

年代:1988

数据来源: MAL

摘要:

ABSTRACTLipid hydrolysis with subsequent production of eicosanoids and lipid peroxidation are two of the earliest potentially pathochemical events induced in spinal cord tissue by mechanical trauma. Although these membrane lipid disturbances are thought to contribute to the paralysis that occur subsequent to spinal cord injury, such a correlation has not been demonstrated directly. Consequently, the purpose of this study was to test the capacity of alpha tocopherol, the major lipid antioxidant in cellular membranes and a compound that limits the injury-induced lipid hydrolysis and peroxidation in spinal cord tissue, to promote functional recovery in a static loading model of spinal cord injury. After laminectomy, the L2 spinal cord of cats was compressed with 180 g for 5 min. For 5 days before injury and for 5 days postinjury, treated cats received orally 1000 IUd-alpha tocopherol acetate daily. Control cats were similarly injured but untreated. All cats were blindly evaluated weekly for 4 weeks for their neurologic recovery based on an 11 point behavioral scale that assessed walking, running, and stair climbing. By the second postinjury week, alpha tocopherol-pretreated cats demonstrated significantly better recovery than untreated controls. By 4 weeks, treated cats had recovered 72% of their preinjury function as compared with 20% for untreated controls, i.e., a 3.5-fold difference. These results strongly suggest that lipid peroxidation and/or hydrolysis is primarily involved in the genesis of posttraumatic paralysis and that alpha tocopherol exerts its protection of injured spinal cord tissue, at least in part, by its antioxidant and/or antilipolytic activity.

ISSN:0897-7151    

DOI:10.1089/neu.1988.5.61

年代:1988

数据来源: MAL

摘要:

ABSTRACTPrevious research (Adametz, 1959) has shown that two-step bilateral lesions of the reticular formation in cats produce minimal behavioral disruption compared to one-step bilateral lesions, which produce profound behavioral suppression. We systematically examined alterations in forebrain acetylcholine (ACh) content and neurologic tolerance to one-step and two-step bilateral and unilateral lesions of the pontomesencephalic reticular formation (PMRF) in rats. One-step and two-step bilateral lesions separated by 1 or 5 days produced irreversible bilateral motor dysfunction. Survival after lesioning was 10%, 20%, and 0%, respectively. Unilateral lesion or two-step bilateral lesions separated by 15 or 30 days produced transient (less than 3 days) contralateral motor dysfunction. Survival after lesioning was 90%, 90%, and 100%, respectively. Within 24 h after one-step bilateral lesions, ACh content was significantly decreased bilaterally in thalamus, frontal cortex, amygdala, hippocampus, and basal forebrain. Within 5 days after unilateral lesioning, ACh content was significantly decreased ipsilaterally in the thalamus, amygdala, and hippocampus and had returned to control values by day 10 in the thalamus and hippocampus. The increased neurologic tolerance and recovery of ACh content in two-step bilateral PMRF lesions demonstrate important functional and neurochemical plasticity to brain injury. Although not directly addressing mechanisms of neural plasticity, this research examined possible associations between neurologic tolerance to PMRF lesions and neurochemical markers of forebrain ACh activity.

ISSN:0897-7151    

DOI:10.1089/neu.1988.5.69

年代:1988

数据来源: MAL

摘要:

ABSTRACTNumerous experimental studies of blunt spinal cord injury have shown that while a variable degree of immediate mechanical damage occurs to spinal blood vessels and axons in proportion to the magnitude of the injury force, a considerable amount of post-traumatic tissue degeneration is due to a secondary pathophysiological process that may be modifiable by appropriate therapeutic intervention. A growing body of biochemical, physiological, and pharmacological evidence has suggested that oxygen free radical-induced lipid peroxidation, working in concert with aberrant calcium fluxes and eicosanoid generation in particular, plays a key role in progressive post-traumatic spinal cord degeneration. Of particular importance, lipid peroxidation has been linked to microvascular damage and hypoperfusion which, if severe enough, can lead to a secondary ischemic insult to the tissue. The ability of intensive dosing with the glucocorticoid steroid methylprednisolone to beneficially affect post-traumatic ischemia and to promote chronic neurologic recovery in spinal cord injured animals has been correlated not with its glucocorticoid activity, but rather with the ability to inhibit post-traumatic spinal lipid peroxidation. In view of this, a novel series of non-glucocorticoid 21-aminosteroids has been developed which lack glucocorticoid activity but are more effective inhibitors of nervous tissue lipid peroxidation than the glucocorticoid steroids. One of these, U74006F, has now been studied in some detail and appears to be a promising new agent for the acute treatment of spinal cord (and brain) trauma. The background and pre-clinical development of this compound to date is reviewed.

ISSN:0897-7151    

DOI:10.1089/neu.1988.5.81

年代:1988

数据来源: MAL