Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System

Abstract

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a “maladaptive” strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.

Optimization of adeno-associated viral vector-mediated transduction of the corticospinal tract: comparison of four promoters

“…The hSYN promoter resulted in neuron-specific transgene expression and this corroborated previous studies using this promoter [21,33,[52][53][54][55][56][57]. One study reported that the synapsin promoter is the most selective promoter among five neuron-specific promoters that were tested in the rat brain [56].…”

“…The AAV1 serotype is commonly used to transduce the CST via intracortical injections [31][32][33][34][35][36][37][38]. An earlier study that compared seven AAV serotypes (AAV1-AAV6, and AAV8) identified AAV1 and AAV5 as the best and secondbest serotypes to transduce the CST in rats [20].…”

Early impoverished environment delays the maturation of cerebral cortex

“…3b,c ). To better analyze sensorimotor coordination, we also evaluated IE rats in the vertical ladder climbing 60 . This motor-specific test showed that IE rats require significantly more time to reach the top surface of the ladder in comparison to SC animals, confirming the general impairment of motor abilities (Fig.…”

Transcranial Direct Current Stimulation (tDCS) in Unilateral Cerebral Palsy: A Pilot Study of Motor Effect

“…Indeed, current knowledge recognizes, as main components of developmental neuroplasticity following perinatal brain injury, both influences of contralateral and ipsilateral corticospinal projections to the paretic hand, and the intrahemispheric and interhemispheric connections of the lesioned and intact motor cortices. It follows that the damaged as well as the intact motor cortex may represent potential central therapeutic targets for tDCS in UCP [9, 15, 16]. It is also important to consider that this neuromodulation tool can modulate the activity and functional connectivity of large-scale brain networks in both hemispheres, even when the stimulating electrode is applied “unilaterally,” over a specific cortical region, such as M1 [15].…”

“…It follows that the damaged as well as the intact motor cortex may represent potential central therapeutic targets for tDCS in UCP [9, 15, 16]. It is also important to consider that this neuromodulation tool can modulate the activity and functional connectivity of large-scale brain networks in both hemispheres, even when the stimulating electrode is applied “unilaterally,” over a specific cortical region, such as M1 [15].…”