Decreased Intracranial Pressure Elevation and Cerebrospinal Fluid Outflow Resistance: A Potential Mechanism of Hypothermia Cerebroprotection Following Experimental Stroke

Abstract

Background: Elevated intracranial pressure (ICP) occurs 18–24 h after ischaemic stroke and is implicated as a potential cause of early neurological deterioration. Increased resistance to cerebrospinal fluid (CSF) outflow after ischaemic stroke is a proposed mechanism for ICP elevation. Ultra-short duration hypothermia prevents ICP elevation 24 h post-stroke in rats. We aimed to determine whether hypothermia would reduce CSF outflow resistance post-stroke. Methods: Transient middle cerebral artery occlusion was performed, followed by gradual cooling to 33 °C. At 18 h post-stroke, CSF outflow resistance was measured using a steady-state infusion method. Results: Hypothermia to 33 °C prevented ICP elevation 18 h post-stroke (hypothermia ∆ICP = 0.8 ± 3.6 mmHg vs. normothermia ∆ICP = 4.4 ± 2.0 mmHg, p = 0.04) and reduced infarct volume 24 h post-stroke (hypothermia = 78.6 ± 21.3 mm3 vs. normothermia = 108.1 ± 17.8 mm3; p = 0.01). Hypothermia to 33 °C did not result in a significant reduction in CSF outflow resistance compared with normothermia controls (0.32 ± 0.36 mmHg/µL/min vs. 1.07 ± 0.99 mmHg/µL/min, p = 0.06). Conclusions: Hypothermia treatment was protective in terms of ICP rise prevention, infarct volume reduction, and may be implicated in CSF outflow resistance post-stroke. Further investigations are warranted to elucidate the mechanisms of ICP elevation and hypothermia treatment.

Age- and time-of-day dependence of glymphatic function in the human brain measured via two diffusion MRI methods

“…Studies have found decreased cerebral blood flow and brain atrophy in aging brains ( Krejza et al, 1999 ; Cao et al, 2022 ). Both the decreased cerebral blood flow and brain atrophy can lead to decreased intracranial pressure ( Krejza et al, 1999 ; Omileke et al, 2021 ), which has also been shown to decrease with age ( Gur et al, 1991 ).…”

Editorial: Cerebrospinal fluid dynamics and intracranial pressure elevation–Novel insights on molecular and physiological mechanisms, and implications for neurological disease

“…ICP elevation due to an increase in fluid build-up in the skull is experienced by patients with large malignant strokes, but this is not usually reported in minor-moderate strokes due to the need for highly invasive ICP measurement methods in the clinic (Helbok et al, 2014 ). Therefore, evidence for ICP elevation and underlying mechanisms in these strokes is mainly derived from pre-clinical stroke models (Omileke et al, 2021a , b ). To further understand these mechanisms, Bothwell et al explored cranial CSF clearance at cervical lymphatics using a tracer method to determine CSF movement into deep cervical lymph nodes and transit to the spinal subarachnoid space in a rat model of ischaemic stroke.…”