Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion

Kuo-Wei Chen; Yong-Ren Chen; Ling-Yu Yang; Ya-Wen Cheng; Sheng-Che Chou; Yi-Hsing Chen; Yi-Tzu Chen; Sung-Tsang Hsieh; Meng-Fai Kuo; Kuo-Chuan Wang

doi:10.1227/neu.0000000000002908

Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion

Neurosurgery. 2024 Mar 21. doi: 10.1227/neu.0000000000002908. Online ahead of print.

Authors

Kuo-Wei Chen^{1

2

3}, Yong-Ren Chen⁴, Ling-Yu Yang¹, Ya-Wen Cheng¹, Sheng-Che Chou^{1

2

5}, Yi-Hsing Chen^{1

2}, Yi-Tzu Chen¹, Sung-Tsang Hsieh^{6

7}, Meng-Fai Kuo¹, Kuo-Chuan Wang¹

Affiliations

¹ Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
² Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
³ Master Degree of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
⁴ Non-invasive Cancer Therapy Research Institute, Taipei, Taiwan.
⁵ Department of Traumatology, National Taiwan University Hospital, National Taiwan University, College of Medicine, Taipei, Taiwan.
⁶ Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
⁷ Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.

PMID: 38511941
DOI: 10.1227/neu.0000000000002908

Abstract

Background and objectives: Hydrocephalus is characterized by progressive enlargement of cerebral ventricles, resulting in impaired microvasculature and cerebral hypoperfusion. This study aimed to demonstrate the microvascular changes in hydrocephalic rats and the effects of cerebrospinal fluid (CSF) release on cerebral blood flow (CBF).

Methods: On postnatal day 21 (P21), male Wistar rats were intracisternally injected with either a kaolin suspension or saline. On P47, Evan's ratio (ER) was measured using MRI. On P49, the arteriolar diameter and vascular density of the pia were quantified using a capillary video microscope. The CBF was measured using laser Doppler flowmetry. The expressions of NeuN and glial fibrillary acidic protein determined by immunochemical staining were correlated with the ER. The CBF and rotarod test performance were recorded before and after CSF release. The expressions of 4-hydroxynonenal (4-HNE) and c-caspase-3 were studied on P56.

Results: Ventriculomegaly was induced to varying degrees, resulting in the stretching and abnormal narrowing of pial arterioles, which regressed with increasing ER. Quantitative analysis revealed significant decreases in the arteriolar diameter and vascular density in the hydrocephalic group compared with those in the control group. In addition, the CBF in the hydrocephalic group decreased to 30%-50% of that in the control group. In hydrocephalus, the neurons appear distorted, and the expression of 4-HNE and reactive astrogliosis increase in the cortex. After CSF was released, improvements in the CBF and rotarod test performance were inversely associated with the ER. In addition, the levels of 4-HNE and c-caspase-3 were further elevated.

Conclusion: Rapid ventricular dilatation is associated with severe microvascular distortion, vascular regression, cortical hypoperfusion, and cellular changes that impair the recovery of CBF and motor function after CSF release. Moreover, CSF release may induce reperfusion injury. This pathophysiology should be taken into account when treating hydrocephalus.

Abstract

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