Voluntary forced use of the impaired limb following stroke facilitates functional recovery in the rat.

Constraint induced movement therapy (CIMT), which forces use of the impaired arm following stroke, improves functional recovery. The mechanisms underlying recovery are not well understood, necessitating further investigation into how rehabilitation may affect neuroplasticity using animal models. Animal motivation and stress make modelling CIMT in animals challenging. We have shown that following focal ischemia, voluntary forced use therapy using pet activity balls could engage the impaired forelimb and result in a modest acceleration in recovery. In this study, we investigated the effects of a more intensive appetitively motivated regimen that included task specific reaching exercises. Adult male Sprague Dawley rats were subjected to focal unilateral stroke using intracerebral injections of endothelin-1 or sham surgery. Three days later, stroke animals were assigned to daily rehabilitation or control therapy. Rehabilitation consisted of 30 min of generalized movement sessions in activity balls, followed by 30 min of voluntary task-specific movement using reaching boxes. Rats were tested weekly to measure forelimb deficit and recovery. After 30 days, animals were euthanized and tissue was examined for infarct volume, brain derived neurotrophic factor expression, and the presence of new neurons using doublecortin immunohistochemistry. Rehabilitation resulted in a significant acceleration of forelimb recovery in several tests, and a significant increase in the number of doublecortin-expressing cells. Furthermore, while the proportion of cells expressing BDNF in the peri-infarct region did not change, there was a shift in the cellular origin of expressed BDNF, resulting in significantly more non-neuronal, non-astrocytic BDNF, presumed to be of microglial origin.

Low-dose neonatal domoic acid causes persistent changes in behavioural and molecular indicators of stress response in rats.

Appropriate stress responses rely on a finely-tuned neuronal balance that must continually adapt to a frequently changing external environment. Alterations in this balance can result in susceptibility to a variety of stress-related disorders, as well as exacerbate already existing conditions. We have previously reported that rat pups injected with a very low dose (20 µg/kg) of domoic acid during the second postnatal week of life display low-grade seizure behaviours when challenged with stressful tasks, and also exhibit a variety of structural and functional changes similar to those seen in temporal lobe epilepsy. The current study was designed to investigate markers of altered stress-response in this model. Following neonatal treatment, adult rats were tested in the elevated plus maze, as well as two water maze tasks, both of which involved a platform reversal challenge. Results indicated a modified behavioural stress/anxiety response, increased perseveration, and alterations in search strategy for all domoate-treated rats, as well as male-specific deficits in cognitive flexibility. In addition, 80% of treated males and 20% of treated females exhibited seizure behaviour. Western blot analysis revealed male-only increases in adrenergic receptor (α2a and α2c) and mineralocorticoid receptor expression, and subtle sex-specific changes in glucocorticoid receptor expression, but no differences in corticotropin-releasing factor receptors I/II, or dopamine D2 receptor expression. A significant decrease in glucocorticoid:mineralocorticoid ratio was also noted. We conclude that early exposure to DOM alters central mechanisms underlying stress response, and that this model may be valuable for investigating the connection between stress and neurological disorders.