Abstract WP299: Encephalomyosynangiosis Promotes Mature Angiogenesis After Ischemic Stroke

Abstract

Backgrounds: Current treatments for ischemic stroke patients is ineffective. The brain's inherent ability to self-heal post ischemic stroke is hampered by inadequate blood supply to the affected region. Encephalomyosynangiosis (EMS), a neurosurgical intervention, has proven successful in promoting angiogenesis in patients with Moyamoya disease. We have earlier shown that EMS can increase angiogenesis after stroke in the implanted region, it is not known if those blood vessels are stable or mature. Given that EMS provide balanced growth factors, we therefore hypothesized that EMS enhances stable or mature cerebral angiogenesis in the cortical region surrounding the muscle graft. Methods: Following a 60-minute period of transient middle cerebral artery occlusion (MCAo), mice were assigned randomly to either MCAo alone or MCAo followed by EMS (3-4 hours post MCAo).. Mice were sacrificed at 7, 21, or 70 days post MCAo. A mouse angiogenesis and proteomic profile array was employed to quantify the expression of angiogenic and neuromodulating proteins. Immunohistochemistry was utilized to visualize the bonding of the graft with the brain cortex, changes in vessel density, and pericyte coverage to assess the degree of normal or mature angiogenesis. Results and Conclusions: Preliminary data indicate successful graft implantation and a significantly increased vessel density (P<0.05 compared to the MCAo alone) in proximity to the muscle graft, signifying increased angiogenesis after stroke. EMS-treated mice exhibited an early improvement in sensory motor deficits post-stroke. Analysis of the angiogenesis and proteomic profile array data unveiled a downregulation of antiangiogenic factors (such as interleukin-10 and Fetuin A) and an upregulation of pro-angiogenic cytokines or growth factors (including Fibroblast Growth Factor and C-X-C Motif Chemokine 12) in the EMS group. Co-immunostaining of the endothelial cell marker (Lectin) with the pericyte marker Platelet-Derived Growth Factor Receptor Beta (PDGFRβ) after 70 days of EMS suggested the stability and maturity of new blood vessels. In summary, the EMS procedure appears effective, holding promise for enhanced stable angiogenesis which may help to expedite recovery following ischemic stroke.