# BLRD Research Career Scientist Award Application > **NIH VA IK6** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2024 · — ## Abstract The overall research program of the applicant has focused on the mechanisms underlying the increased risk and worsened outcome of ischemic stroke in individuals with type 2 diabetes mellitus (T2DM) with a long- term goal of finding therapies to improve blood perfusion and reduce secondary brain damage among these patients. My current research program is an extension of a novel finding made from my lab showing that mice with T2DM exhibited impaired leptomeningeal (LMA) collateral flow after stroke using optical imaging, mirroring the finding in stroke patients with metabolic syndrome using CT-angiography. Through multiphoton imaging we observed an increased leukocyte-platelet aggregates in the cerebral arterioles and increased leukocyte rolling in cerebral veins following ischemic stroke in T2DM mice compared to normoglycemic control mice. These events suggest that T2DM promotes neuroinflammation and formation of microthrombi after stroke and contributes to poor cerebral perfusion and collateral flow. The applicant’s lab has made another crucial discovery that T2DM mice exhibited defective type I and type II interferon signaling response, which attenuates the induction of neuroprotective effect mediated by Toll-Like receptors. Since it is well known that age diminishes the ability of many clinical therapies in inducing tolerance to ischemia, understanding the pathological mechanisms contributing to the failure of ischemic preconditioning in T2DM may have a wide- reaching impact on current clinically available conditioning paradigms that induce ischemic tolerance. To that end, the projects to be pursued during the proposed funding period of this RCS award are as follows: 1). The current funded Merit Review grant of the applicant will determine the underlying pathological mechanisms by which T2DM-induced chronic inflammation dampens the therapeutic effect of ischemic tolerance induction. The goal is to find critical targets to overcome the interferon signaling defect in T2DM and restore ischemic conditioning response. 2). To investigate how chronic inflammation caused by T2DM exacerbates stroke induced secondary brain injury, we will determine the functional role of complement components such as the anaphylatoxin receptors C3ar/C5ar, elevated in T2DM prior to stroke, in enhancing the transmigration of peripheral immune cells after stroke. Our study will also discern whether T2DM chronically affects brain resident myeloid cells and increases their potential in attacking neurons and synapses after stroke. 3). To determine the therapeutic efficacy of interventions based on pharmacological, behavioral, or electrical stimulation in restoring neural regeneration, brain connectivity and function after ischemic stroke. The research proposed for the next funding period will continue to support the mission of VA Healthcare through studies that will facilitate the translational development of potential therapeutic interventions in improving stroke outcome amo... ## Key facts - **NIH application ID:** 10920251 - **Project number:** 2IK6BX004600-06 - **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO - **Principal Investigator:** JIALING LIU - **Activity code:** IK6 (R01, R21, SBIR, etc.) - **Funding institute:** VA - **Fiscal year:** 2024 - **Award amount:** — - **Award type:** 2 - **Project period:** 2019-04-01 → 2029-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10920251 ## Citation > US National Institutes of Health, RePORTER application 10920251, BLRD Research Career Scientist Award Application (2IK6BX004600-06). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10920251. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*