Research

Current Research Projects

Role of Purinergic receptor P2X4 in stroke injury

Following a stroke, a burst of ATP is released from dying brain cells which further activates both neurons and microglial purinergic receptor P2X4 (P2X4R) to mediate fast excitatory neurotransmission via cation influx. Excessive activation of P2X4R causes the release of several pro-inflammatory cytokines at the early time point of ischemic injury. However, contrary to the effects of acute activation, chronic inhibition or absence of this receptor may impair stroke recovery. Therefore, given this dual temporal role of P2X4R in ischemic injury, we are systematically exploring for its therapeutic potential in post-stroke recovery.

Stroke model and P2X4R mediated immune infiltration in ischemic stroke

Encephalomyosynangiosis for stroke recovery

Stepwise illustration of EMS surgery after MCAo:

Encephalomyosynangiosis (EMS) is a neurosurgical procedure with low morbidity that is applied to promote collateral vascular formation in patients with moyamoya disease, a condition with progressive narrowing of cranial arteries and consequent low blood flow that increases risk for ischemic stroke. The procedure involves placement of a temporalis muscle flap on ischemic brain tissue. Human data suggest that extensive collateral formation occurs within a few months after EMS in patients with moyamoya disease. Therefore, it was hypothesized that EMS, which provides a local and robust tissue as a source of vascular endothelium and angiogenic growth factors, will supply growth factors for angiogenesis that could promote neuronal survival following ischemic stroke. As a proof of concept, we have established EMS surgery for  the first time in mice after ischemic stroke. Preliminary data from this model show that EMS surgery temporalis muscle graft was bonded to the cortical surface after 21 days. Additionally, mice receiving EMS after stroke show increased lectin-positive blood vessel formation compared to stroke mice that did not receive EMS. These data indicate that EMS may be a safe and feasible treatment to restore blood
supply to ischemic tissue; however, more in-depth, longer-term studies are needed. Therefore, this model will be used to further investigate EMS for treating ischemic stroke in the following overall to determine
if EMS promotes angiogenesis after non-moyamoya ischemic stroke, and to determine if EMS promotes long-term functional recovery after non-moyamoya ischemic stroke. This project is highly innovative and expected outcomes will benefit several research areas. If successful, this concept could ultimately impact the treatment of non-moyamoya ischemic stroke, a condition with high
prevalence in the US.

EMS surgery (4hrs after MCAo) increases blood vessel density in ischemic lesions after 21 days of stroke.

Testing novel miRNA inhibitors for the treatment of stroke

MicroRNAs (miRNAs) are short non-coding RNAs and have emerged as a powerful intervention tool for many diseases including stroke. They regulate a broad spectrum of biological pathways through fine-tuning of protein expression levels and altering gene expression levels. miRNA can concurrently target multiple effectors of pathways involved in stroke pathology. In this project we focus on the differential expression of miRNA expressed in mice after stroke and determine if blocking (with genetic deletion or antagomirs) or enhancing (mimics) these target miRNAs modulate their effects.  In addition, we are trying to develop novel  gamma PNA based  miRNA inhibitor therapy  to improve functional recovery after stroke.

Schematics in vivo work flow after treatment with miRNA inhibitor in mice after ischemic stroke