Neuronal Circuit Remodeling in the Contralateral Cortical Hemisphere during Functional Recovery from Cerebral Infarction

Abstract

Recent advances in functional imaging of human brain activity in stroke patients, e.g., functional magnetic resonance imaging, have revealed that cortical hemisphere contralateral to the infarction plays an important role in the recovery process. However, underlying mechanisms occurring in contralateral hemisphere during functional recovery have not been elucidated. We experimentally induced a complete infarction of somatosensory cortex in right hemisphere of mice and examined the neuronal changes in contralateral (left) somatosensory cortex during recovery. Both basal and ipsilateral somatosensory stimuli-evoked neuronal activity in left (intact) hemisphere transiently increased 2 d after stroke, followed by an increase in the turnover rate of usually stable mushroom-type synaptic spines at 1 week, observed by using two-photon imaging in vivo. At 4 weeks after stroke, when functional recovery had occurred, a new pattern of electrical circuit activity in response to somatosensory stimuli was established in intact ipsilateral hemisphere. Thus, the left somatosensory cortex can compensate for the loss of the right somatosensory cortex by remodeling neuronal circuits and establishing new sensory processing. This finding could contribute to establish the effective clinical treatments targeted on the intact hemisphere for the recovery of impaired functions and to achieve better quality of life of patients.

Optogenetic neuronal stimulation promotes functional recovery after stroke

“…S3), suggesting that stimulation-induced increases in neurotrophins are dependent on the stroke environment. These increases in neurotrophins, possibly resulting from the interactions between the two hemispheres after stimulation, further confirms the involvement of the contralesional cortex in the stroke recovery process (6,42,43). It is also possible that the increases in neurotrophins are related to the contralesional limb movement during M1 stimulation (Movie S1), as this movement can send signals back to contralesional and ipsilesional cortices (44,45).…”

Absence of Large-Scale Dendritic Plasticity of Layer 5 Pyramidal Neurons in Peri-Infarct Cortex

“…For instance, changes in the density or turnover of dendritic spines, which have been documented in peri-infarct cortex, are likely to play a major role in circuit plasticity after stroke (Brown et al, 2009;Mostany et al, 2010). In addition, changes in spine turnover appear to also take place in the contralateral hemisphere (Takatsuru et al, 2009), suggesting that, even in the intact hemisphere, plasticity at the level of single synapses is more likely to contribute to functional recovery after stroke than large-scale remodeling of entire dendritic arbors. Future in vivo imaging studies should confirm whether rehabilitative strategies (Biernaskie and Corbett, 2001;Gibb et al, 2010) or manipulations of certain signaling pathways, such as PTEN or fibroblast growth factor (Rowntree and Kolb, 1997), might induce dendritic remodeling after stroke.…”

Brain Plasticity Following Ischemia: Effect of Estrogen and Other Cerebroprotective Drugs

“…In addition, several subsequent studies have shown dendritic and axonal reorganization after experimental brain ischemia with dynamic changes of synaptic density in the injured brain region (Benowitz and Carmichael, 2010;Brown et al, 2010;Lu et al, 2004;Mostany et al, 2010;Scheff et al, 2005;Sulkowski et al, 2006;Takatsuru et al, 2009;etc.). The most active neuronal regeneration occurs up to 2-3 weeks after brain injury (Blizzard et al 2011;Jones and Schallert, 1992), which provides a wide therapeutic window in cerebral ischemia.…”

“…Nevertheless up to two weeks after stroke dendritic density and turnover increases in the peri-infarct cortex and also in the contralateral hemisphere, which plays a major role in brain regeneration (Brown et al, 2010;Mostany et al, 2010;Takatsuru et al, 2009). In addition, following cardiac arrest decreased microtubule-associated protein 2 (MAP-2) expression was detected in the rat reflecting lower dendritic density (Sulkowski et al, 2006).…”