Abstract
Background
Hydrocephalus is a common neurosurgical condition with significant limitations in traditional treatment methods. The glymphatic system, an emerging concept, has an unclear role in hydrocephalus. This study focuses on exploring the glymphatic system and its regulatory mechanisms in post-intraventricular hemorrhage (IVH) hydrocephalus, particularly the crucial role and mechanisms of the CCL2/CCR2 signaling pathway. The aim is to provide new targets and strategies for the treatment of hydrocephalus.
Methods
An IVH mouse model was used to induce hydrocephalus. CCR2 was knocked down through viral transfection techniques, and various experimental methods, including cerebrospinal fluid (CSF) tracing, ultrastructural observation, MRI imaging, and immunofluorescence analysis, were employed to evaluate its effects on hydrocephalus.
Results
The study found that the distribution of fluid components in the brain changes after IVH, and harmful metabolites accumulate in the brain, leading to neurological dysfunction and hydrocephalus. Knocking down CCR2 restored the polarization of aquaporin 4 (AQP4), improved glymphatic system (GS) dysfunction, and significantly alleviated the progression of hydrocephalus in IVH mice. CSF flow tests and tracer experiments confirmed that inhibiting CCR2 could restore CSF flow and remove of harmful metabolites. Additionally, inhibiting CCR2 significantly improved motor and cognitive functions in IVH mice.
Conclusion
This study suggests that CCR2 plays a crucial role in the occurrence and development of hydrocephalus after IVH. Knocking down CCR2 can reduce endoplasmic reticulum stress, restore AQP4 polarization, improve GS function, and thereby alleviate hydrocephalus and restore neurological function.