Theresa D. Hernandez

Recovery of function after brain damage: Severe and chronic disruption by diazepam

Following unilateral damage to the anterior-medial region of the neocortex (AMC) in rats a sensory asymmetry appeared, but recovered within a week. In a separate group of rats with AMC lesions daily 3-week exposure to diazepam (Valium, 5 mg/kg) beginning 12 h after surgery caused recovery to be delayed indefinitely. The efficiency and speed (as opposed to symmetry) of behavior was not impaired. More than 9 weeks after discontinuation of diazepam (12 weeks postsurgery), recovery was still not apparent. Postmortem analysis ruled out lesion size as a contributing factor. In a second experiment undrugged animals with AMC lesions were allowed to recover for at least 3 weeks before being exposed to diazepam. These animals showed only a transient (2-day) reinstatement of asymmetry despite continuous drug treatment. We conclude that important mechanisms serving recovery of function may be vulnerable during a short period soon after brain damage.

Seizures and recovery from experimental brain damage

The effects of the gamma-aminobutyric acid antagonist, pentylenetetrazol (PTZ), on recovery from somatosensory and motor asymmetries after unilateral sensorimotor cortex lesions were investigated. Behavior was assessed using a bilateral tactile stimulation test and a measure of forelimb motor coordination. Immediately after surgery, the PTZ-treated and saline (SAL) control groups both exhibited severe ipsilateral behavioral asymmetries. Rats receiving PTZ recovered significantly faster from somatosensory asymmetry than those receiving SAL. Recovery was complete in the PTZ group within 3 postoperative weeks, while the SAL group failed to reach a comparable level until 2 months after surgery. There was no difference between PTZ and SAL groups on recovery of forelimb motor coordination. No difference in lesion size between the SAL and the PTZ groups could be found. These data are consistent with the hypothesis that post-traumatic neuronal depression may contribute to the severity of sensorimotor deficits observed after brain damage.

Graft-derived recovery from 6-OHDA lesions: specificity of ventral mesencephalic graft tissues.

SummaryA series of experiments have been conducted to assess the specificity of recovery from motor asymmetries that is provided by dopamine-rich grafts in the neostriatum of rats with unilateral dopamine-depleting lesions produced by injection of 6-hydroxydopamine into the ascending nigrostriatal pathway. Grafts of embryonic tissue taken from the substantia nigra (rich in dopamine neurons) could provide a complete recovery of methamphetamine-induced rotation and a partial recovery of apomorphine-induced rotation, whereas no recovery was seen in rats with grafts of tissue rich in another monoamine (serotonin, dissected from the mesencephalic raphe) or of tissue appropriate to the target (dissected from the striatal eminence). 6-Hydroxydopamine lesions of dopamine cells in the grafts of recovered animals reinstated the initial lesion-induced asymmetry. Dopamine-rich grafts implanted into the intact neostriatum did not induce any “supernormal” asymmetry in the rats, but did provide a “prophylactic” protection against subsequent lesions of the intrinsic ipsilateral dopamine nigrostriatal system. Post-mortem biochemical assays indicated that the extent of dopamine depletion in the neostriatum of lesioned rats correlated highly with both methamphetamine and apomorphine turning rates. Similarly, both drug rotation tests correlated significantly with the extent of dopamine restoration in the dorsal striatum of rats with dopamine-rich grafts, the correlation being significantly higher for the methamphetamine than for the apomorphine test.

Reconsidering the Link Between Impulsivity and Suicidal Behavior

It is widely accepted that suicidal behavior often occurs with little planning. We propose, however, that suicidal behavior is rarely if ever impulsive—that it is too frightening and physically distressing to engage in without forethought—and that suicidal behavior in impulsive individuals is accounted for by painful and fearsome behaviors capable of enhancing their capacity for suicide. We conducted a meta-analysis of the association between trait impulsivity and suicidal behavior and a critical review of research considering the impulsiveness of specific suicide attempts. Meta-analytic results suggest the relationship between trait impulsivity and suicidal behavior is small. Furthermore, studies examining a mediating role of painful and provocative behaviors have uniformly supported our model. Results from our review suggest that researchers have been unable to adequately measure impulsivity of attempts and that measures sensitive to episodic planning must be developed to further our understanding of this phenomenon.

PREVENTING POST – TRAUMATIC EPILEPSY AFTER BRAIN INJURY: WEIGHING THE COSTS AND BENEFITS OF ANTICONVULSANT PROPHYLAXIS

If the primary goal in the treatment of traumatic brain injury is the minimization of post-injury morbidity, treatment strategies that effectively prevent the development of post-traumatic epilepsy and have a beneficial (or at least neutral) impact on functional recovery are necessary. Here, Theresa Hernandez discusses the degree to which the current post-injury practice of anticonvulsant prophylaxis satisfies each of these criteria.

Disruption of behavioral recovery by the anti-convulsant phenobarbital.

The effects of the anti-convulsant phenobarbital on recovery of function was assessed. Phenobarbital, which is frequently administered to humans after brain injury, was injected for 7 days beginning 48 h after unilateral cortex lesions in rats. Recovery from somatosensory deficits was significantly delayed in phenobarbital treated animals. These results provide additional evidence that anti-convulsants interfere with recovery when administered after brain damage.

Relationship of agonist efficacy to changes in GABA sensitivity and anticonvulsant tolerance following chronic benzodiazepine ligand exposure

Benzodiazepine ligands of differing efficacy including the agonist, diazepam, the partial agonist, Ro 16-6028 and the antagonist, Ro 15-1788, were administered in vivo to rats continuously for 3 weeks. The magnitude of change in various measures of GABA sensitivity could be correlated directly with increasing agonist efficacy: maximal changes were seen following chronic treatment with diazepam, intermediate changes were seen following the partial agonist Ro 16-6028 and no changes were observed following chronic Ro 15-1788 administration. The magnitude of change could also be correlated with increasing potential for tolerance development to anticonvulsant efficacy following chronic exposure to these benzodiazepine ligands.

Attitudes Toward Complementary and Alternative Medicine Influence Its Use

OBJECTIVE The aim of this study was to explore how attitudes toward complementary and alternative medicine (CAM) and conventional medicine influence CAM use in a healthy population, and how health locus of control and exercise further affect CAM use. DESIGN A cross-sectional survey design was used. PARTICIPANTS The sample consisted of 65 healthy graduate students. MAIN OUTCOME MEASURES Since previous studies have focused on the attitudes of medical providers toward CAM, there are currently no standard, widely used measures of attitudes toward CAM from the perspective of the healthcare recipient. Thus, a new measure, the Complementary, Alternative, and Conventional Medicine Attitudes Scale (CACMAS) was created to address how attitudes of healthcare recipients affect CAM use. The Multidimensional Health Locus of Control Scale (MHLC) was used to investigate effects of health locus of control on CAM use, and participants reported which of 17 listed CAM treatments they had used in the past, were currently using, or would likely use in the future. Participants also reported days of exercise in the past month to explore if those engaging in healthy behaviors might report more CAM use. RESULTS Having a philosophical congruence with CAM and agreement with holistic balance was associated with increased CAM use. Dissatisfaction with conventional medicine was also related to increased CAM use, but to a lesser extent. Those attributing health to personal behaviors (an internal health locus of control) reported more CAM use, as did those engaging in more resistance training in the previous month.

Seizures, epilepsy, and functional recovery after traumatic brain injury: a reappraisal

Traumatic brain injury is an epidemic in the United States, with an estimated incidence of 2 million cases per year, of which almost 500,000 are admitted to the hospital.lZ2 In addition, the survival rates after brain injury are on the rise.3 As a result, brain injury has become an increasing problem in this country. Its major sequelae, post-traumatic epilepsy and functional disability, impose a high cost t o society and the individual survivors in terms of acute health care, rehabilitation, extended care, and anticonvulsant drug therapy. Furthermore, the resulting epilepsy and physical impairments are associated with inability to return to social isolation, and failure to resume leisure ac t iv i t ie~ .~ .~ Finally, traumatic brain injury creates a high economic burden that costs approximately

Effect of amygdala kindling on the in vivo release of GABA and 5-HT in the dorsal raphe nucleus in freely moving rats

25 billion per year,l and the long-term costs associated with this condition undoubtedly contribute to much of this expense. Previous research on traumatic brain injury has largely examined the issues of post-traumatic epilepsy and functional outcome as separate entities. However, emerging data indicate that these problems are inextricably intertwined. As we review, there are complex interactions between mechanisms of functional brain recovery and the genesis of post-traumatic epilepsy. Although the nature of brain injury influences functional outcome and the probability of epileptogenesis, an increasing body of evidence indicates the presence or absence of seizures, their temporal presentation with respect to brain injury, and that administration of anticonvulsant drugs may have profound effects on functional recovery. Because these variables may be modified by medical therapy, it is important to better understand their interactions to maximally improve the outcome in persons who sustain traumatic brain injury. Several series from civilian and military populations have identified risk factors for post-traumatic epilepsy. We recently reviewed specific risk factors c~mprehensively.~ To summarize briefly, it is clear that the greatest predictor of post-traumatic epilepsy is the severity of the injury.8-10 In cases of the most severe parenchymal injuries, the frequency of posttraumatic epilepsy approaches or exceeds 50%.11J2 Because both the worst neurologic deficits and highest frequency of post-traumatic epilepsy occur in the most severely brain-injured persons, it is not surprising that the expression of seizures has not been extensively examined as an independent factor in analyses of functional recovery.