Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia

Abstract

Deep brain stimulation (DBS) has been tentatively explored to promote motor recovery after stroke. Stroke could transiently activate endogenous self-repair processes, including neurogenesis in the subventricular zone (SVZ). In this regard, it is of considerable clinical interest to study whether DBS of the lateral cerebellar nucleus (LCN) could promote neurogenesis in the SVZ for functional recovery after stroke. In the present study, rats were trained on the pasta matrix reaching task and the ladder rung walking task before surgery. And then an electrode was implanted in the LCN following cortical ischemia induced by endothelin-1 injection. After 1 week of recovery, LCN DBS coupled with motor training for two weeks promoted motor function recovery, and reduced the infarct volumes post-ischemia. LCN DBS augmented poststroke neurogenetic responses, characterized by proliferation of neural progenitor cells (NPCs) and neuroblasts in the SVZ and subsequent differentiation into neurons in the ischemic penumbra at 21 days poststroke. DBS with the same stimulus parameters at 1 month after ischemia could also increase nascent neuroblasts in the SVZ and newly matured neurons in the perilesional cortex at 42 days poststroke. These results suggest that LCN DBS promotes endogenous neurogenesis for neurorestoration after cortical ischemia.

Effects of Lateral Cerebellar Nucleus Stimulation on Seizures in Rats Kindled to Different Levels of Seizure Severity with PTZ

“…It might be assumed that GABAergic PC efferents do not contribute to such prevention. That is why other pathways of cerebellar participation in seizure modulation might be signi cant [11,44,45]. Additionally, less marked reduction of PC at the early stage of PTZ kindling does not exclude their involvement in myoclonus pathogenesis and the facilitation of myoclonus with LCN ES.…”

Targeting the Erk1/2 and autophagy signaling easily improved the neurobalst differentiation and cognitive function after young transient forebrain ischemia compared to old gerbils

“…Cerebral injury caused by transient forebrain ischemic stroke leads to cognitive dysfunctions, and this process is accompanied by elevated neurogenesis in the neurogenic niches of the postnatal brain [ 50 , 51 ]. Many studies have already been suggested that the neurogenesis, including cell proliferation and differentiation of neuroblasts into mature neurons by some stimuli, is the key role to promote neurological rehabilitation and cognitive dysfunction in some common neurodegenerative diseases, including stroke in rodents [ 52 , 53 ]. In the present study, our results demonstrated that the capability of neurogenesis in young gerbils after long-term I/R injury is directly proportional to the recovery of neurological function and cognitive ability, on the contrary, this capability of old gerbils is obviously insufficient.…”

Low-Intensity Focused Ultrasound Neuromodulation for Stroke Recovery: A Novel Deep Brain Stimulation Approach for Neurorehabilitation?

“…157 Sarica et al (2022) recently published their work in an ex-vivo setting regarding appropriate parameters for TUS to enhance adaptability of such applications and to not produce hazardous temperatures on DBS lead. 157 Alternatively, non-invasive stimulation 65,241,242 but also invasive 63,65,242 stimulation of the cerebellum has been tried out for post-stroke recovery. Preclinical studies proved DBS stimulation to the cerebellum for post-stroke conditions to be effective in rodents.…”

“…Invasive approaches, especially deep brain stimulation (DBS), have been discussed for stroke recovery due to promising preclinical results suggesting their potential for neurorehabilitation in patients. 19,[61][62][63][64][65] Accordingly, a first preclinical, invasive study showed that neuromodulation of the dentate nucleus via DBS improved stroke recovery. 65 DBS of the cerebellar dentate nucleus (DN) [66][67][68] has also led to improved motor recovery, probed in a firstin-human trial (NCT02835443).…”