Abstract
Focal cortical stroke often leads to persistent motor deficits, prompting the need for more effective interventions. The efficacy of rehabilitation can be increased by 'plasticity-stimulating' treatments that enhance experience-dependent modifications in spared areas. Transcallosal pathways represent a promising therapeutic target, but their role in post-stroke recovery remains controversial. Here, we demonstrate that the contralesional cortex exerts an enhanced interhemispheric inhibition over the perilesional tissue after focal cortical stroke in mouse forelimb motor cortex. Accordingly, we designed a rehabilitation protocol combining intensive, repeatable exercises on a robotic platform with reversible inactivation of the contralesional cortex. This treatment promoted recovery in general motor tests and in manual dexterity with remarkable restoration of pre-lesion movement patterns, evaluated by kinematic analysis. Recovery was accompanied by a reduction of transcallosal inhibition and 'plasticity brakes' over the perilesional tissue. Our data support the use of combinatorial clinical therapies exploiting robotic devices and modulation of interhemispheric connectivity.
Highlights
Focal cortical stroke in motor cortex often leads to persistent motor deficits that strongly impact the patients’ quality of life
A focal ischemic lesion was induced in the primary motor cortex (M1) of mice, targeting the caudal forelimb area (CFA) by means of Rose Bengal-induced phototrombosis (Lai et al, 2015; Alia et al, 2016)
In a minority of the mice, partial damage was detected in the dorsal aspect of the white matter, as demonstrated by reduced staining for myelin basic protein (MBP; Figure 1a, inset)
Summary
Focal cortical stroke in motor cortex often leads to persistent motor deficits that strongly impact the patients’ quality of life. It should be noted that, unlike primates and humans, rodents do not have direct cortico-motoneuronal connections as the fastest pyramidal connections are dysinaptic (Alstermark and Ogawa, 2004; Alstermark and Pettersson, 2014) In this manuscript, we define a rehabilitation protocol to promote ‘true’ recovery of motor function (i.e., the restoration of pre-lesion movement patterns) after focal cortical stroke in mice (Lai et al, 2015). Silencing of the contralesional cortex was coupled with training in a robotic device, the M-Platform (designed on the basis of one of the first human rehabilitation robots, the ArmGuide, Reinkensmeyer et al, 2000) that allows intensive and highly repeatable exercises of the mouse forelimb (Spalletti et al, 2014) Such combined treatment normalized transcallosal inhibition and promoted recovery in general motor tests and in manual dexterity (i.e. skilled reaching) with a remarkable restoration of pre-lesion movement patterns
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