Differences in functional immune responses of high vs. low hardy healthy individuals.

An association between the personality trait of hardiness and immune responses was explored. Blood samples were collected from 21 healthy individuals under nonstressful conditions, who had either high or low levels of hardiness. Functional immune assays tested for natural killer (NK) cell activity and proliferation responses to Candida albicans (Candida), purified protein derivative from Mycobacterium tuberculosis (PPD), lipopolysaccharide (LPS), concanavalin A (Con A), and Staphylococcus enterotoxin A (Staph A). Differences between high and low hardy groups on these immune responses were examined using Bonferroni adjusted independent t-tests. Results revealed significant differences between the groups for Candida, PPD, Con A, and Staph A. In all instances, the high hardy group had larger mean proliferative responses than the low hardy group. Implications of the study as well as avenues for future research are discussed.

Intracisternal basic fibroblast growth factor enhances functional recovery and up-regulates the expression of a molecular marker of neuronal sprouting following focal cerebral infarction.

Focal cerebral infarction (stroke) due to unilateral occlusion of the middle cerebral artery in mature rats produces deficits in sensorimotor function of the contralateral limbs that recover partially over time. We found that biweekly intracisternal injection of basic fibroblast growth factor (bFGF; 0.5 microg/injection), a potent neurotrophic polypeptide, markedly enhanced recovery of sensorimotor function of the contralateral limbs during the first month after stroke without apparent adverse side effects. Immunostaining for growth-associated protein 43 (GAP-43), a molecular marker of axonal sprouting, showed a selective increase in GAP-43 immunoreactivity in the intact sensorimotor cortex contralateral to cerebral infarcts following bFGF treatment. These results show that bFGF treatment can enhance functional recovery after stroke, and that the mechanism may include stimulation of neuronal sprouting in the intact brain.

Use-dependent structural events in recovery of function.

We described research suggesting that forelimb use is essential for marked neural growth in the intact cortex after unilateral forelimb-cortical lesions. Although unilateral brain injury can cause severe functional impairment, the injury may be capable of mobilizing potent resources for compensatory changes such as dendritic arborization in the noninjured hemisphere, but only for a limited period of time and only with appropriate behavioral pressure. Unexpectedly, surviving tissue in the injured hemisphere may be fatally vulnerable to excessive behavioral demand. If the impaired limb is overused because the nonimpaired limb is restricted by a one-sleeve cast, injury size is greatly increased and recovery of function is severely disrupted. It is hypothesized that behaviorally driven neurotransmitter release relating to forced use of the forelimb may be toxic to surviving tissue that has been partially traumatized by the lesion. These data and hypotheses are summarized in Fig. 7. The "use-it-or-lose-it" rehabilitative approach is popular, but perhaps a less aggressive strategy should be adopted for optimal restoration of function in the injured hemisphere. Whereas traditional experiments on mechanisms of recovery of function are designed specifically to determine potentially compensatory neural changes that might mediate behavioral outcome, these experiments support a quite different view of the interplay between neural and behavioral events: behavioral changes may directly alter anatomical events.