Michael E. Carey

Oxidative stress following traumatic brain injury in rats

BACKGROUND Free radicals may be involved in the pathophysiology of traumatic brain injury (TBI) through oxidative damage of neurovascular structures. Endogenous antioxidants, such as ascorbate and alpha-tocopherol, may play a critical role in combating these oxidative reactions and their oxidized products can serve as an important index of oxidative stress. METHODS We used electron spin resonance (ESR) spectroscopy and in vivo spin trapping (reaction of an organic compound with free radical species) to detect the possible generation of free radicals after TBI. Injury was inflicted by a weight drop technique over the head (5.7 kg-cm). Rats were intravenously infused with either 1 mL, 0.1 M of the spin trap, alpha-phenyl-N-tert-butyl nitrone (PBN), or an equivalent volume of saline immediately before TBI or sham-injury. Animals were divided into four groups: (1) Group I: PBN-infused sham-injured, (2) Group II: PBN-infused injured, (3) Group III: saline-infused sham-injured, and (4) Group IV: saline-infused injured. Additional groups of saline-infused uninjured, saline-infused, and PBN-infused injured animals were used for histopathology. Sixty minutes after TBI or sham-injury, rats were again anesthetized and decapitated. The brains were removed within 1 minute, homogenized, and extracted for lipids. The extracts were analyzed by ESR spectroscopy. Brain ascorbic acid (AA) concentration was determined spectrophotometrically, using the ascorbate oxidase assay. RESULTS No PBN spin adduct signals (indicating trapped free radical species) were visible 60 minutes after TBI. All groups of rats showed an ascorbyl free radical signal. The ascorbyl signal intensity (AI) was, however, significantly higher in the injured rats, while the brain (AA) was significantly reduced. In addition, the ratio of AI/AA, which eliminates the effect of variable ascorbate concentrations in the brain, was also significantly higher in the injured animals. CONCLUSIONS We conclude that 60 minutes following TBI there was a significantly increased level of oxidative stress in the brain. This may reflect formation of free radical species with subsequent interaction with ascorbate (antioxidant) during the 60 minute period. The lack of PBN spin adduct signals 1 hour after TBI may indicate that free radical generation is time dependent and might be detectable earlier or later than the 60 minute period.

Traumatic brain injury of the forelimb and hindlimb sensorimotor areas in the rat: physiological, histological and behavioral correlates.

This study characterizes physiological, histological and behavioral effects of traumatic brain injury (TBI) produced by a controlled pneumatic impactor striking the entire right sensorimotor cortex of the anesthetized rat. Damage to both the fore- and hindlimb sensorimotor areas resulted in a hemiparetic animal which allowed us to use four sensitive behavioral/neurological tests to track the recovery sequelae after injury. Initial experiments measured cardiovascular and respiratory effects after cortical impact which depressed the dura to varying depths. Both 0.5 mm and 1 mm cortical depressions produced a momentary decrease (P < 0.05) in mean arterial blood pressure (MABP) while cortical impacts to depths of 2 mm or 3 mm produced a momentary increase (P < 0.05) in MABP. Normotension was re-established within 30 s after the initial response at all injury levels. Respiratory rate was affected only following 3 mm cortical depressions. A 1 mm cortical depression appeared ideal in terms of minimal cardiorespiratory effects, low mortality and lasting behavioral effects. For behavioral and histologic studies, therefore, additional rats were injured by a 1 mm cortical impact and tested for 8 weeks after TBI using four behavioral tests. Injured rats displayed both fore- and hindlimb deficits up to 56 days while traversing a narrow beam (P < 0.001) and up to 28 days when crossing a pegged beam (P < 0.05). Forelimb deficits evaluated on a wire grid platform were evident for 28 days (P < 0.05). Forepaw preference measured in a non-test setting indicated a bias to use the unaffected forepaw for 35 days (P < 0.05). A biphasic pattern of functional recovery was seen on all tests. A period of rapid functional recovery lasting 7 to 10 days was followed by a slower period of functional recovery lasting many weeks. Possible meanings of this biphasic recovery are discussed as issues of behavioral compensation/adaptation versus true neural recovery. Eight weeks after TBI histological analyses indicated that axonal degeneration was present in the areas adjacent to the ipsilateral cortical injury site. Degenerating fibers also extended across the corpus callosum into the homologous area in the contralateral cortex and were seen in the ipsilateral striatum, somatosensory and motor thalamic nuclei and substantia nigra. Significant axonal degeneration occurred bilaterally around the deep cerebellar nuclei. Degenerating fibers extended into the folia and terminated in the cerebellar granule cell layer. Thus the entire sensorimotor control system appeared to have been affected by a cortical injury.

Intrathecal morphine pump as a treatment option in chronic pain of nonmalignant origin

BACKGROUND Implantable pumps for the delivery of intrathecal morphine have become a common option for administering opiate medication for the management of pain in patients with terminal cancer. Options for treating chronic pain of non-malignant origin are more controversial. This study describes responses to intrathecal morphine administration for managing chronic pain in patients without an underlying malignancy. METHODS Eleven patients between the ages of 29 and 81 years, nine with failed back syndrome (FBS) and two with neuropathic pain (NP) from other causes, were chosen from 15 consecutive individuals referred to neurosurgery clinic. The presenting levels of pain and a functional-economic outcome level were determined for each patient. Patients were admitted to the hospital for therapeutic trials and were assessed for the appropriateness of their analgesic response and for adverse responses to the medication. A morphine pump was implanted in five males and six females who were followed for up to 3 years. RESULTS A good to excellent analgesic response was seen in 8 (73%) patients (6 FBS; 2 NP). In the remaining three patients (27%), the analgesic response was judged poor (3 FBS). In patients with FBS, the total effective response was 67%. Two patients experienced bladder dysfunction requiring pump removal. Other adverse effects of pump placement were rare. CONCLUSIONS The morphine pump was found to be a viable alternative in the management of failed back syndrome. Its use in long-term therapy, however, is not without limitations and should be a last choice option.

Ladder beam and camera video recording system for evaluating forelimb and hindlimb deficits after sensorimotor cortex injury in rats

Hindlimb and forelimb deficits in rats caused by sensorimotor cortex lesions are frequently tested by using the narrow flat beam (hindlimb), the narrow pegged beam (hindlimb and forelimb) or the grid-walking (forelimb) tests. Although these are excellent tests, the narrow flat beam generates non-parametric data so that using more powerful parametric statistical analyses are prohibited. All these tests can be difficult to score if the rat is moving rapidly. Foot misplacements, especially on the grid-walking test, are indicative of an ongoing deficit, but have not been reliably and accurately described and quantified previously. In this paper we present an easy to construct and use horizontal ladder-beam with a camera system on rails which can be used to evaluate both hindlimb and forelimb deficits in a single test. By slow motion videotape playback we were able to quantify and demonstrate foot misplacements which go beyond the recovery period usually seen using more conventional measures (i.e. footslips and footfaults). This convenient system provides a rapid and reliable method for recording and evaluating rat performance on any type of beam and may be useful for measuring sensorimotor recovery following brain injury.

The Sinking Bullet

We report a case of a missile injury to the brain with an unusual complication. The bullet migrated by its mere weight to a distant location through the brain parenchyma after it initially lodged in a superficial site. Instances of similar phenomena reported in the literature are reviewed.

Ballistic helmets and aspects of their design

THE HEAD REPRESENTS approximately 9% of the body area exposed in combat yet receives approximately 20% of all “hits.” The desirability of protecting this vital structure would appear self-evident. Helmet design is a complex issue. Factors that designers of United States Army helmets thoughtfully consider include weight, ballistic qualities of the construction material, balance, helmet-to-person interface (comfort), maintenance of vision and hearing, equipment and weapon compatibility, ease of modification, available materials and manufacturing techniques, durability, ease of decontamination, disposability, and cost. The envisioned future role of the infantryman will make the interplay among these factors even more daunting.

Focal brain injury and its effects on cerebral mantle, neurons, and fiber tracks

Following a mild cortical impact injury delivered by a piston to the right sensorimotor cortex of the anesthetized rat, we evaluated mantle loss, neuronal changes, and fiber track degeneration by deOlmos silver stains up to 8 weeks after injury. Darkened neurons indicating damage (chromatolysis) occurred widely throughout both hemispheres and were seen from 1 h to 8 weeks after injury. This effect might have occurred from pressure wave damage from piston impact, brain displacement or deafferentation. Cerebral mantle loss was variable but fiber track degeneration related to projection and corticofugal descending tracks associated with the right sensorimotor system was rather constant. Unexpectedly, considerable fiber track degeneration occurred within the cerebellum, especially the inferior vermis. Cells directly under the piston face were surprisingly well-preserved but axon degeneration studies showed that these apparently intact neuronal cell bodies were surrounded by a dense network of degenerating fiber tracks. The intact cells, therefore, may have been functionally cut off from the rest of the brain owing to interruption of their efferents and afferents. The increased susceptibility of axons compared to cell bodies seen with this focal injury is similar to that observed with diffuse brain injury. The early appearing, severe and widespread axon damage we observed suggests that amelioration of focal traumatic brain injury will have to be directed promptly to the preservation of axons as well as cell bodies.

Effects of the "special bomb": recollections of a neurosurgeon in Hiroshima, August 8-15, 1945.

THIS ARTICLE RECOUNTS neurosurgeon Lieutenant Colonel Hideo (Shimada) Kishis experience when he was appointed as chief of the First Investigation Committee that evaluated the damage caused by the atom bomb dropped on Hiroshima.

Reference memory and allocentric spatial localization deficits after unilateral cortical brain injury in the rat

Traumatic brain injury (TBI) produces learning and memory impairments in humans. This study investigated the effects of TBI on memory and spatial localization strategies in rats. Prior to TBI, separate groups of rats were trained in an 8-arm radial maze with either all 8 arms baited (Expt. 1) or only 4 of the 8 arms baited (Expt. 2). TBI was produced by a controlled pneumatic impactor striking the entire right sensorimotor cortex of the anesthetized rat. Rats used in Expt. 1 were selected because they did not use a stereotypic response strategy (going to adjacent arms) in performing the maze before injury. After TBI the rats were not different from control rats in the number of working memory (WM) errors made. They did, however, display a distinct propensity to go to adjacent arms, i.e., exhibit stereotypic behavior, with a right-handed (ipsiversive) bias (P < 0.005). After TBI, rats which were trained with only 4 of 8 arms baited committed more reference memory (RM) errors than control rats (P < 0.05). They did not differ from controls on WM errors. Injured rats took longer to re-attain criteria than controls (P < 0.0001). Injured rats also initially displayed a propensity to enter the adjacent arm sequentially before re-attaining criteria. Further analysis indicated that injured rats re-learned the maze with a right-hand bias (P < 0.0001). The results of both experiments suggest that after TBI, rats shifted from an allocentric to an egocentric strategy to re-learn the maze. It was suggested that damage to the parietal cortex may have been responsible for both RM errors and the shift away from an allocentric strategy to an egocentric strategy. Possibly, the ipsiversive (right-hand) bias may be the result of a behaviorally or injury-induced neurochemical asymmetry within the motor system.

The treatment of wartime brain wounds: traditional versus minimal debridement.

BACKGROUND Since World War II, surgeons in Western armies dealing with brain wounds have generally advocated thorough missile track debridement, and many have urged meticulous dural closure to prevent cerebral spinal fluid (CSF) leakage and subsequent infection. For the last decade some reports have appeared wherein wartime brain wounds have been treated by minimal brain debridement with little or no attention to tight dural closure. This report compares and contrasts postdebridement complications reported with each method. METHODS I reviewed the pertinent neurosurgical papers from Vietnam, the Israeli war in Lebanon, and the Iran-Iraq war and compared the results of traditional debridement and water-tight dural closure to those following minimal debridement without close attention to dural closure. RESULTS Minimal brain debridements without tight dural closure were up to 20 to 30 times more likely to require additional debridement, had a 10-15 times higher incidence of life-threatening CSF leakage, a fivefold increase in postdebridement meningitis, and a 2.5 times greater risk of fatal meningitis. CONCLUSIONS Compared to thorough brain debridement and watertight dural closure, minimal debridements and nonwatertight dural closure give inferior results.