TY - JOUR
T1 - Altered Cerebrospinal Fluid Clearance and Increased Intracranial Pressure in Rats 18 h After Experimental Cortical Ischaemia
AU - Bothwell, Steven W.
AU - Omileke, Daniel
AU - Hood, Rebecca J.
AU - Pepperall, Debbie Gai
AU - Azarpeykan, Sara
AU - Patabendige, Adjanie
AU - Spratt, Neil J.
N1 - Funding Information:
Thanks to Brett Graham at the University of Newcastle for demonstrating the laminectomy technique and to Nikolce Mackovski for training SB in surgical procedures and providing technical assistance throughout experiments. We would like to thank Christopher Oldmeadow, of the CReDITSS Unit, Hunter Medical Research Institute, for biostatistical advice. Figure 7 was created with BioRender.com. Funding. This study was supported by an HDR scholarship to SB by the University of Newcastle, Australia. AP was supported by the NSW Ministry of Health under the NSW Health Early-Mid Career Fellowships Scheme. NS was supported by a co-funded Australian NHMRC/National Heart Foundation Career Development/Future Leader Fellowship (GNT1110629/100827).
Publisher Copyright:
© Copyright © 2021 Bothwell, Omileke, Hood, Pepperall, Azarpeykan, Patabendige and Spratt.
PY - 2021/8/9
Y1 - 2021/8/9
N2 - Oedema-independent intracranial pressure (ICP) rise peaks 20–22-h post-stroke in rats and may explain early neurological deterioration. Cerebrospinal fluid (CSF) volume changes may be involved. Cranial CSF clearance primarily occurs via the cervical lymphatics and movement into the spinal portion of the cranio-spinal compartment. We explored whether impaired CSF clearance at these sites could explain ICP rise after stroke. We recorded ICP at baseline and 18-h post-stroke, when we expect changes contributing to peak ICP to be present. CSF clearance was assessed in rats receiving photothrombotic stroke or sham surgery by intraventricular tracer infusion. Tracer concentration was quantified in the deep cervical lymph nodes ex vivo and tracer transit to the spinal subarachnoid space was imaged in vivo. ICP rose significantly from baseline to 18-h post-stroke in stroke vs. sham rats [median = 5 mmHg, interquartile range (IQR) = 0.1–9.43, n = 12, vs. −0.3 mmHg, IQR = −1.9–1.7, n = 10], p = 0.03. There was a bimodal distribution of rats with and without ICP rise. Tracer in the deep cervical lymph nodes was significantly lower in stroke with ICP rise (0 μg/mL, IQR = 0–0.11) and without ICP rise (0 μg/mL, IQR = 0–4.47) compared with sham rats (4.17 μg/mL, IQR = 0.74–8.51), p = 0.02. ICP rise was inversely correlated with faster CSF transit to the spinal subarachnoid space (R = −0.59, p = 0.006, Spearman’s correlation). These data suggest that reduced cranial clearance of CSF via cervical lymphatics may contribute to post-stroke ICP rise, partially compensated via increased spinal CSF outflow.
AB - Oedema-independent intracranial pressure (ICP) rise peaks 20–22-h post-stroke in rats and may explain early neurological deterioration. Cerebrospinal fluid (CSF) volume changes may be involved. Cranial CSF clearance primarily occurs via the cervical lymphatics and movement into the spinal portion of the cranio-spinal compartment. We explored whether impaired CSF clearance at these sites could explain ICP rise after stroke. We recorded ICP at baseline and 18-h post-stroke, when we expect changes contributing to peak ICP to be present. CSF clearance was assessed in rats receiving photothrombotic stroke or sham surgery by intraventricular tracer infusion. Tracer concentration was quantified in the deep cervical lymph nodes ex vivo and tracer transit to the spinal subarachnoid space was imaged in vivo. ICP rose significantly from baseline to 18-h post-stroke in stroke vs. sham rats [median = 5 mmHg, interquartile range (IQR) = 0.1–9.43, n = 12, vs. −0.3 mmHg, IQR = −1.9–1.7, n = 10], p = 0.03. There was a bimodal distribution of rats with and without ICP rise. Tracer in the deep cervical lymph nodes was significantly lower in stroke with ICP rise (0 μg/mL, IQR = 0–0.11) and without ICP rise (0 μg/mL, IQR = 0–4.47) compared with sham rats (4.17 μg/mL, IQR = 0.74–8.51), p = 0.02. ICP rise was inversely correlated with faster CSF transit to the spinal subarachnoid space (R = −0.59, p = 0.006, Spearman’s correlation). These data suggest that reduced cranial clearance of CSF via cervical lymphatics may contribute to post-stroke ICP rise, partially compensated via increased spinal CSF outflow.
KW - cerebrospinal fluid
KW - infarct expansion
KW - intracranial pressure
KW - ischaemia
KW - lymphatics
KW - neurological deterioration
KW - spinal clearance
KW - stroke
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UR - http://www.scopus.com/inward/citedby.url?scp=85113783002&partnerID=8YFLogxK
U2 - 10.3389/fnmol.2021.712779
DO - 10.3389/fnmol.2021.712779
M3 - Article (journal)
AN - SCOPUS:85113783002
SN - 1662-5099
VL - 14
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
M1 - 712779
ER -