Critical Role of the Astrocyte for Functional Remodeling in Contralateral Hemisphere of Somatosensory Cortex after Stroke

Abstract

After ischemic stroke, the corresponding area contralateral to the lesion may partly compensate for the loss of function. We previously reported the remodeling of neuronal circuits in the contralateral somatosensory cortex (SSC) during the first week after infarction for processing bilateral information, resulting in functional compensation. However, the underlying processes in the contralateral hemisphere after stroke have not yet been fully elucidated. Recent studies have shown that astrocytes may play critical roles in synaptic reorganization and functional compensation after a stroke. Thus, we aim to clarify the contribution of astrocytes using a rodent stroke model. In vivo calcium imaging showed a significantly large number of astrocytes in the contralateral SSC responding to ipsilateral limb stimulation at the first week after infarction. Simultaneously, extracellular glutamine level increased, indicating the involvement of astrocytes in the conversion of glutamate to glutamine, which may be an important process for functional recovery. This hypothesis was supported further by the observation that application of (2S,3S)-3-{3-[4-(trifluoromethyl)benzoylamino]benzyloxy} aspartate, a glial glutamate transporter blocker, disturbed the functional recovery. These findings indicate the involvement of astrocytes in functional remodeling/recovery in the area contralateral to the lesion. Our study has provided new insights into the mechanisms underlying synaptic remodeling after cerebral infarction, which contributes to the development of effective therapeutic approaches for patients after a stroke.

Optogenetic neuronal stimulation promotes functional recovery after stroke

“…Although electrical stimulation and transcranial magnetic stimulation show promise in promoting recovery (17,18), these techniques are limited by imprecision and indiscriminate activation or inhibition of all cell types near the stimulated site; thus, they can produce undesired effects such as psychiatric and motor/speech problems (19)(20)(21). In addition, it has been difficult to elucidate the cell type and mechanisms driving recovery, as multiple cell types such as neurons, astrocytes, and oligodendrocytes have been shown to contribute to remodeling and recovery processes after stroke (5,(22)(23)(24)(25)(26)(27).…”

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

“…Nevertheless, these brain stimulation techniques have been shown to promote recovery when stimulating the ipsilesional cortex and their noninvasive application is a major advantage, as cortical excitability can be modulated in a painless procedure [43,69,70]. However, these techniques are limited by imprecise and indiscriminate activation or inhibition of all cell types near the stimulated site, thus they can stimulate multiple cell types, such as neurons, astrocytes, and oligodendrocytes, which have all been shown to affect remodeling and recovery [71][72][73][74][75]. Furthermore, specific excitatory or inhibitory circuit modulations are nearly impossible with these techniques.…”

Ca2+ Signaling in Astrocytes and its Role in Ischemic Stroke

“…To study the role of astrocytes in the functional recovery in contralateral hemisphere, Takatsuru et al performed in vivo Ca 2+ imaging to examine the neuronal and astrocytic Ca 2+ responses in the region contralateral to the site of stroke at different times following PT (Takatsuru et al 2013). The results showed that the number of astrocytes with a response to limb stimulation was small in the sham group, but in the stroke groups the number was significantly increased in the contralateral somatosensory cortex responding to ipsilateral limb stimulation at the first and second week after infarction.…”

“…A significantly larger number of astrocytes responded only to the single-limb stimulation in the sham group as compared with stroke groups, but a smaller number of astrocytes responded to multiple-limb stimulation in the sham group as compared to the stroke groups. Interestingly, unlike neurons, astrocytes showed no preference in response to contralateral and ipsilateral limb stimulation (Takatsuru et al 2013). The peak amplitude of Ca 2+ response was also increased in stroke groups.…”