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

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.

Ultra-Short Duration Hypothermia Prevents Intracranial Pressure Elevation Following Ischaemic Stroke in Rats

There is a transient increase in intracranial pressure (ICP) 18–24 h after ischaemic stroke in rats, which is prevented by short-duration hypothermia using rapid cooling methods. Clinical trials of long-duration hypothermia have been limited by feasibility and associated complications, which may be avoided by short-duration cooling. Animal studies have cooled faster than is achievable in patients. We aimed to determine whether gradual cooling at a rate of 2°C/h to 33°C or 1°C/h to 34.5°C, with a 30 min duration at target temperatures, prevented ICP elevation and reduced infarct volume in rats. Transient middle cerebral artery occlusion was performed, followed by gradual cooling to target temperature. Hypothermia to 33°C prevented significant ICP elevation (hypothermia ΔICP = 1.56 ± 2.26 mmHg vs normothermia ΔICP = 8.93 ± 4.82 mmHg; p = 0.02) and reduced infarct volume (hypothermia = 46.4 ± 12.3 mm3 vs normothermia = 85.0 ± 17.5 mm3; p = 0.01). Hypothermia to 34.5°C did not significantly prevent ICP elevation or reduce infarct volume. We showed that gradual cooling to 33°C, at cooling rates achievable in patients, had the same ICP preventative effect as traditional rapid cooling methods. This suggests that this paradigm could be translated to prevent delayed ICP rise in stroke patients.

Two different indications of ventriculoperitoneal and cystoperitoneal shunting in six dogs

In this study we described two different indications of ventriculo- and cystoperitoneal shunting (VPS, CPS) procedures in six dogs, including their clinical data and magnetic resonance imaging (MRI) examinations. One dog had moderate and two dogs had severe congenital hydrocephalus, one was presented with intracranial pressure elevation due to meningoencephalitis of unknown origin (MUO) associated with congenital hydrocephalus, and two with quadrigeminal cysts (QC). VPS procedures were done in four and CPS in two dogs, using low-pressure valve systems. The follow-up period ranged from 1 to 6 months and control MRI scans were also made. Significant improvement was detected in five cases during the short-term follow-up period (1 month) and in four cases in the medium-term follow-up (2–6 months). Major complications were found in two cases: one dog with acute-hypertensive hydrocephalus died one week after surgery, and in another case development of a chronic subdural haematoma and hygroma caused death 3 months after the surgery. Minor complications (e.g. subdural hygroma) were found in two cases. In cases of severe hydrocephalus or intracranial cysts, higher-pressure valve systems are recommended in order to prevent subdural hygroma. Transient postoperative clinical signs usually resolve within one week after the surgery.

Author Correction: Characterization of Retinal Ganglion Cell and Optic Nerve Phenotypes Caused by Sustained Intracranial Pressure Elevation in Mice

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Intracranial pressure elevation alters CSF clearance pathways

BackgroundInfusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models.MethodsWe used a two-compartment model consisting of the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate, capillaries and paravascular spaces, resistances were calculated and used to estimate flow before and during an infusion test. Next, pressure in the subarachnoid space and paravascular spaces were computed. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters.ResultsAt baseline, we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, paravascular flow reversed and 25% of the fluid left through these spaces, while 60% went through the arachnoid granulations and only 15% through the cribriform plate.ConclusionsThe relative distribution of CSF flow to different clearance pathways depends on intracranial pressure (ICP), with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space.

Rapid Brain Death following Cardiac Arrest without Intracranial Pressure Rise and Cerebral Circulation Arrest

We describe here an unusual case of brain death following cardiac arrest. Brain electric activity had totally ceased, allowing the confirmation of brain death, despite normal cerebral blood flow (assessed by both transcranial doppler and tomodensitometry) and no evidence of intracranial hypertension. In our case, a residual electric activity was assessed at admission and lesions worsened on imaging during ICU stay, suggesting that part of the neuronal damage occurred after brain reperfusion. All these elements suggest BD rather by cellular toxicity than intracranial pressure elevation.