Acute inactivation of the contralesional hemisphere for longer durations improves recovery after cortical injury

Abstract

A rapidly growing number of studies using inhibition of the contralesional hemisphere after stroke are reporting improvement in motor performance of the paretic hand. These studies have used different treatment onset time, duration and non-invasive methods of inhibition. Whereas these results are encouraging, several questions regarding the mechanisms of inhibition and the most effective treatment parameters are currently unanswered. In the present study, we used a rat model of cortical lesion to study the effects of GABA-mediated inactivation on motor recovery. In particular, we were interested in understanding better the effect of inactivation duration when it is initiated within hours following a cortical lesion. Cortical lesions were induced with endothelin-1 microinjections. The contralesional hemisphere was inactivated with continuous infusion of the GABA-A agonist Muscimol for 3, 7 or 14days in three different groups of animals. In a fourth group, Muscimol was infused at slower rate for 14days to provide additional insights on the relation between the effects of inactivation on the non-paretic forelimb behavior and the recovery of the paretic forelimb. In spontaneously recovered animals, the lesion caused a sustained bias to use the non-paretic forelimb and long-lasting grasping deficits with the paretic forelimb. Contralesional inactivation produced a general decrease of behavioral activity, affected the spontaneous use of the forelimbs and caused a specific reduction of the non-paretic forelimb function. The intensity and the duration of these behavioral effects varied in the different experimental groups. For the paretic forelimb, increasing inactivation duration accelerated the recovery of grasping function. Both groups with 14days of inactivation had similar recovery profiles and performed better than animals that spontaneously recovered. Whereas the plateau performance of the paretic forelimb correlated with the duration of contralesional inactivation, it was not correlated with the spontaneous use of the forelimbs or with grasping performance of the non-paretic hand. Our results support that contralesional inactivation initiated within hours after a cortical lesion can improve recovery of the paretic forelimb. In our model, increasing the duration of the inactivation improved motor outcomes but the spontaneous use and motor performance of the non-paretic forelimb had no impact on recovery of the paretic forelimb.

Early and Moderate Sensory Stimulation Exerts a Protective Effect on Perilesion Representations of Somatosensory Cortex after Focal Ischemic Damage

“…did not differ between 9 and 14 days after the lesion induction, respectively. This result corroborates previous studies using cortical compression or endothelin-1 to induce a restricted ischemic infarct to the S1 cortex which showed that cell death increase during the early postlesion days, is at a maximum at 3–5 days and does not evolve over the subsequent days and weeks [31], [32], [33], [34].…”

Motor System Reorganization After Stroke: Stimulating and Training Toward Perfection

“…However, the contralesional dendritic growth in layer V pyramidal neurons that we have observed has no known benefit (83), and contralesional M1 activity can have disruptive influences on paretic limb function (47, 126,134,141). Sprouting can also be maladaptive.…”

Molecular, cellular and functional events in axonal sprouting after stroke

“…These implications are clinically important because the phenomenon of “learned nonuse,” or heightened reliance on the good limb after stroke, is a common sequelae to hemiparesis, but may hinder circuit repair and motor recovery. The effect of the contralateral cortex on recovery was also shown to be negative in blocking study: muscimol inactivation of the contralesional cortex for 3–14 days improves behavioral outcome (Mansoori et al, 2014). This data indicates that in different animal models of stroke, the contralateral (to the stroke) cortex has been shown to both mediate recovery and to impede recovery.…”