Cerebellum KCC2 protein expression plasticity in response to cerebral cortical stroke

Recent evidence suggests extra-cortical adaptations within the cerebellum may contribute to motor recovery in patients with cortical ischemic strokes. The molecular/cellular adaptations enabling this effect to have not been identified. Chloride transport proteins (NKCC1 and KCC2) are important regulators of neuronal transmission and may underlie adaptive changes following ischemic stroke.

Examine changes in cerebellar NKCC1 and KCC2 protein expression following cortical ischemic stroke.

Adult C57BL/6J male mice underwent sham or the left middle cerebral artery occlusion (tMCAo)-induced ischemic stroke. Changes of NKCC1 and KCC2 proteins within the deep cerebellar nuclei (DCN) were assessed by immunofluorescence staining.

tMCAo induced selective infarct lesion in the left striatum and cortex of the stroke mice but not in other brain regions including cerebellum. The inwardly directed chloride transporter NKCC1 was equivocally expressed within bi-hemispheric DCN of both sham control and stroke mice. In contrast, the outwardly directed chloride transporter KCC2 protein expression was significantly higher in the bi-hemispheric DCN of stroke brains, compared to sham controls. Double immunostaining analysis revealed a statistically significant increase in KCC2 intensity within VGLUT-1⁺ neurons of the ipsilateral DCN of the stroke mice, but not in the VGAT⁺ neurons.

Ischemic cortical stroke stimulates KCC2 protein expression in the DCN VGLUT-1⁺ neurons, without a change in NKCC1 protein expression.