Based upon neurophysiologic, neuroanatomic, and neuroimaging studies conducted over the past two decades, the cerebral cortex can now be viewed as functionally and structurally dynamic. More specifically, the functional topography of the motor cortex (commonly called the motor homunculus or motor map), can be modified by a variety of experimental manipulations, including peripheral or central injury, electrical stimulation, pharmacologic treatment, and behavioral experience. The specific types of behavioral experiences that induce long-term plasticity in motor maps appear to be limited to those that entail the development of new motor skills. Moreover, recent evidence demonstrates that functional alterations in motor cortex organization are accompanied by changes in dendritic and synaptic structure, as well as alterations in the regulation of cortical neurotransmitter systems. These findings have strong clinical relevance as it has recently been shown that after injury to the motor cortex, as might occur in stroke, post-injury behavioral experience may play an adaptive role in modifying the functional organization of the remaining, intact cortical tissue.

Role of adaptive plasticity in recovery of function after damage to motor cortex

Background and Purpose—d-Amphetamine administration increases behavioral recovery after various cortical lesions including cortical ablations, contusions, and focal ischemia in animals and after st...

Enhanced Neocortical Neural Sprouting, Synaptogenesis, and Behavioral Recovery With d-Amphetamine Therapy After Neocortical Infarction in Rats

Recovery after damage to motor cortical areas.

Background and Purpose— A number of studies suggest that drugs which increase the release of norepinephrine promote recovery when administered late (days to weeks) after brain injury in animals. A small number of clinical studies have investigated the effects of the noradrenergic agonist dextroamphetamine in patients recovering from motor deficits following stroke. To determine whether these findings extend to communication deficits subsequent to stroke, we administered dextroamphetamine, paired with speech/language therapy, to patients with aphasia. Methods— In a prospective, double-blind study, 21 aphasic patients with an acute nonhemorrhagic infarction were randomly assigned to receive either 10 mg dextroamphetamine or a placebo. Patients were entered between days 16 and 45 after onset and were treated on a 3-day/4-day schedule for 10 sessions. Thirty minutes after drug/placebo administration, subjects received a 1-hour session of speech/language therapy. The Porch Index of Communicative Ability was us...

http://www.strokecenterdallas.org/strk01.pdf

A Double-Blind, Placebo-Controlled Study of the Use of Amphetamine in the Treatment of Aphasia

Statins administered postischemia promote functional improvement in rats, independent of their capability to lower cholesterol. We therefore tested the effect of statin treatment on traumatic brain injury (TBI) in rats. Atorvastatin was orally administered (1 mg/kg/day) to Wistar rats starting 1 day after TBI for 7 consecutive days. Control animals received saline. Modified Neurological Severity Scores and Corner tests were utilized to evaluate functional response to treatment. Bromodeoxyuridine (BrdU, 100 mg/kg) was also intraperitoneally injected daily for 14 consecutive days to label the newly generated endothelial cells. Rats were sacrificed at day 14 after TBI, and the brain samples were processed for immunohistochemical staining. Atorvastatin administration after brain injury significantly reduced the neurological functional deficits, increased neuronal survival and synaptogenesis in the boundary zone of the lesion and in the CA3 regions of the hippocampus, and induced angiogenesis in these regions. The results suggest that atorvastatin may provide beneficial effects in experimental TBI.

Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury.

The effects of amphetamine on the recovery of function following unilateral lesions of the rat somatic sensorimotor cortex (SMC) were examined. Rats with large SMC were tested on two measures of locomotor placing: the beam-walking test and the foot-fault test. Amphetamine produced an immediate and enduring facilitation of recovery on the beam-walking test. In contrast, the drug had no effect on the rats' ability to accurately place the forelimbs on the rungs of the elevated grid during locomotion on the foot-fault test. These data suggest that amphetamine may facilitate recovery when the requirements of the task produce a deficit in the initiation of locomotion but not when the animal is required to use somatosensory and proprioceptive cues to guide performance on the task. A second group of rats with smaller SMC lesions was evaluated with tactile-placing tests and the bilateral-tactile stimulation task. The forelimb placing reaction is elicited by unilateral tactile stimulation of the vibrissae or forelimb, whereas the ipsilateral asymmetry observed on the bilateral-tactile stimulation test has been interpreted as an impairment in processing stimuli presented on both sides of the body. On two measures of forelimb placing amphetamine produced a facilitation of recovery, but restoration of function was not observed during the period of drug intoxication. In contrast, amphetamine had no effect on recovery of function on the bilateral-tactile stimulation test. Taken together, these data suggest that the behavioral requirements of the task are an important factor in determining the facilitatory effects of amphetamine on recovery of function.

T.D. Schmanke

Papers

The effects of amphetamine on recovery of function after cortical damage in the rat depend on the behavioral requirements of the task.