Chronic hypertension alters cerebrovascular function, which can lead to neurovascular pathologies and increased susceptibility to neurological disorders. The purpose of this study was to utilize in vivo MRI methods with corroborating immunohistology to evaluate neurovascular dysfunction due to progressive chronic hypertension. The spontaneously hypertensive rat (SHR) model at different stages of hypertension was studied to evaluate: i) basal cerebral blood flow (CBF), ii) cerebrovascular reactivity (CVR) assessed by CBF and blood-oxygenation level dependent (BOLD) signal changes to hypercapnia, iii) neurovascular coupling from CBF and BOLD changes to forepaw stimulation, and iv) damage of neurovascular unit (NVU) components (microvascular, astrocyte and neuron densities). Comparisons were made with age-matched normotensive Wistar Kyoto (WKY) rats. In 10-week SHR (mild hypertension), basal CBF was higher (p < 0.05), CVR trended higher, and neurovascular coupling response was higher (p < 0.05), compared to normotensive rats. In 40-week SHR (severe hypertension), basal CBF, CVR, and neurovascular coupling response were reversed to similar or below normotensive rats, and were significantly different from 10-week SHR (p < 0.05). Immunohistological analysis found significantly reduced microvascular density, increased astrocytes, and reduced neuronal density in SHR at 40 weeks (p < 0.05) but not at 10 weeks (p > 0.05) in comparison to age-matched controls. In conclusion, we observed a bi-phasic basal CBF, CVR and neurovascular coupling response from early to late hypertension using in vivo MRI, with significant changes prior to changes in the NVU components from histology. MRI provides clinically relevant data that might be useful to characterize neurovascular pathogenesis on the brain in hypertension.

慢性高血压会改变脑血管功能，从而导致神经血管病变并增加对神经系统疾病的易感性。本研究的目的是利用具有确证免疫组织学的体内 MRI 方法来评估由于进行性慢性高血压引起的神经血管功能障碍。对高血压不同阶段的自发性高血压大鼠 (SHR) 模型进行研究以评估：i) 基础脑血流量 (CBF)，ii) 通过 CBF 评估的脑血管反应性 (CVR) 和血氧水平依赖性 (BOLD) 信号变化至高碳酸血症，iii) 从 CBF 和 BOLD 变化到前爪刺激的神经血管耦合，以及 iv) 神经血管单元 (NVU) 组件（微血管、星形胶质细胞和神经元密度）的损伤。与年龄匹配的正常血压 Wistar 京都 (WKY) 大鼠进行了比较。在 10 周的 SHR（轻度高血压）中，与血压正常的大鼠相比，基础 CBF 更高（p < 0.05），CVR 趋势更高，神经血管耦合反应更高（p < 0.05）。在 40 周 SHR（重度高血压）中，基础 CBF、CVR 和神经血管耦合反应逆转为血压正常或低于正常大鼠，并且与 10 周 SHR 有显着差异（p < 0.05）。免疫组织学分析发现，与年龄匹配的对照相比，SHR 在 40 周（p < 0.05）时显着降低微血管密度、星形胶质细胞增加和神经元密度降低（p < 0.05），但在 10 周时没有（p > 0.05）。总之，我们使用体内 MRI 观察到从早期到晚期高血压的双相基础 CBF、CVR 和神经血管耦合反应，在组织学 NVU 成分发生变化之前发生了显着变化。