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Hanscom-Trofy, Y.

Publications and source records attributed to Hanscom-Trofy, Y..

2 recordsLinked to original sources

Anatomical Identification and Pressure Myography of the Rat Middle Cerebral Artery: A Comprehensive Protocol for Diverse Genetic Models

The middle cerebral artery (MCA) is critical for cerebral blood flow autoregulation and a primary site of cerebrovascular pathology in stroke, Alzheimers disease, and vascular dementia. Pressure myography enables precise ex vivo quantification of MCA structure and function, but requires accurate anatomical identification and careful vessel handling to ensure reproducibility across diverse rat genetic models. This chapter provides a comprehensive, step-by-step protocol for isolating and cannulating the rat MCA M2 segment for pressure myography. We detail precise anatomical landmarks to ensure consistent vessel selection across strains. The protocol includes optimized solutions, cannulation techniques, and pressure protocols validated across multiple rat models, including transgenic (TgF344-AD), diabetic (T2DN), consomic (SS.5BN, FHH.1BN), and genome-edited strains. Extensive troubleshooting notes address common technical challenges, including vessel viability assessment, pressure integrity, and strain-specific autoregulatory ranges. This methodology bridges molecular genetic findings with fundamental cerebrovascular physiology, enabling researchers to characterize myogenic reactivity, passive mechanical properties, and structural remodeling in rat models of cerebrovascular disease.

physiology↗

Inhibition of Soluble Epoxide Hydrolase Rescues Cognitive Deficits by Preserving Neurovascular Integrity and Attenuating Glial- and Neuropathology in Diabetic-Related Dementia

Diabetes mellitus (DM) is a major risk factor contributing to the development of Alzheimers disease-related dementias (ADRD). While one of the early symptoms of both Alzheimers disease (AD) and DM-related ADRD is a reduction in cerebral blood flow, the underlying biological mechanisms driving this decline remain to be fully elucidated. Genome-wide association studies have linked AD/ADRD to single-nucleotide polymorphisms in the gene encoding soluble epoxide hydrolase (sEH), an enzyme we previously reported to be upregulated in the brains of an AD rat model. Our previous work also demonstrated that chronic inhibition of sEH with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) preserves hippocampal-dependent spatial learning and memory and improves cerebral hemodynamics in both AD and DM-ADRD models. In the present study, we found that chronic TPPU treatment (1 mg/kg/day for 9 weeks) reduced brain sEH expression, improved cortical-based long-term non-spatial recognition memory involving both cortical and hippocampal networks, and reduced anxiety in DM-ADRD rats. TPPU improved brain perfusion and normalized impaired whisker-evoked functional hyperemia, an effect linked to upregulation of Kir2.1 expression in cerebral capillaries. Furthermore, TPPU restored tight junction proteins (ZO-1 and OCLN), mitigated capillary rarefaction, and suppressed astrocyte and microglial activation. At the cellular level, TPPU attenuated hippocampal neurodegeneration, restored the expression of synaptic proteins (PSD95 and SY38), and reduced levels of key pro-inflammatory chemokines, including MCP-1, RANTES, and MIP-1, in DM-ADRD. In conclusion, TPPU preserves cognitive function in DM-ADRD by mitigating cerebrovascular dysfunction, neuroinflammation, and gliosis while protecting synaptic integrity and neuronal survival, representing a promising therapeutic strategy for DM-ADRD.

neuroscience↗