Mild hypothermia alleviates brain oedema and blood-brain barrier disruption by attenuating tight junction and adherens junction breakdown in a swine model of cardiopulmonary resuscitation

Abstract

Mild hypothermia improves survival and neurological recovery after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). However, the mechanism underlying this phenomenon is not fully elucidated. The aim of this study was to determine whether mild hypothermia alleviates early blood–brain barrier (BBB) disruption. We investigated the effects of mild hypothermia on neurologic outcome, survival rate, brain water content, BBB permeability and changes in tight junctions (TJs) and adherens junctions (AJs) after CA and CPR. Pigs were subjected to 8 min of untreated ventricular fibrillation followed by CPR. Mild hypothermia (33°C) was intravascularly induced and maintained at this temperature for 12 h, followed by active rewarming. Mild hypothermia significantly reduced cortical water content, decreased BBB permeability and attenuated TJ ultrastructural and basement membrane breakdown in brain cortical microvessels. Mild hypothermia also attenuated the CPR-induced decreases in TJ (occludin, claudin-5, ZO-1) and AJ (VE-cadherin) protein and mRNA expression. Furthermore, mild hypothermia decreased the CA- and CPR-induced increases in matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression and increased angiogenin-1 (Ang-1) expression. Our findings suggest that mild hypothermia attenuates the CA- and resuscitation-induced early brain oedema and BBB disruption, and this improvement might be at least partially associated with attenuation of the breakdown of TJ and AJ, suppression of MMP-9 and VEGF expression, and upregulation of Ang-1 expression.

Neonatal excitotoxicity modifies blood‐brain barrier properties increasing its susceptibility to hypertonic shock in adulthood

“…Furthermore, neonatal MSG treatment also reduced the protein expression level of ZO‐1 in the CMC and Hp in adulthood (Figure 1b). Reduced expression of ZO‐1 has been observed during increased BBB permeability, as part of the early response to hypoxic episodes (Li et al, 2017) or status epilepticus (Kim, Ko, Hyun, & Kang, 2015). Then, the decreased protein expression level of claudin‐5 and ZO‐1 observed in MSG‐treated CMC, and Hp (Figure 1a,b) is consistent with the high susceptibility of these regions to HS.…”

Hypertonic saline infusion suppresses apoptosis of hippocampal cells in a rat model of cardiopulmonary resuscitation

“…A large body of evidence shows that hypertonic saline can significantly reduce intracranial pressure and enhance cerebral perfusion pressure 29 , whether in the early phase of post-ischemic global cerebral cell edema or in the later phase of vasogenic brain edema induced by impaired blood brain barrier 30 . HS was shown to be superior to mannitol, a traditional dehydrating agent, in attenuating cerebral edema, and working longer 31 .In addition, disruption of blood brain barrier was shown to play a major role in CA- induced brain injury by causing cerebral vascular insult 32 . The close association of cerebral edema and brain neuronal cell apoptosis with increased permeability of blood brain barrier is well-documented 33 .…”

Principios éticos de la reanimación cardiopulmonar y cerebral

“…Deben estar presentes entre distintos tipos de reanimadores (legos o profesionales), pueden estar relacionados con el inicio o la culminación del apoyo vital básico o avanzado y pueden estar influenciadas por factores individuales, de la cultura local e internacional, legal, de la tradición, religiosa, social y económica. Estas situaciones de emergencia vital hacen más difícil la toma de decisiones (13)(14)(15)(16)(17) . Se deben guiar por los conocimientos científicos, las preferencias de las personas, por la normativa local y los requisitos legales siempre basados en los principios básicos de la ética.…”

“…Europa por el European Resuscitation Council quien adecua las recomendaciones sobre RCP del ILCOR a las condiciones y peculiaridades del continente (17)(18)(19)(20) .…”

“…Estos principios han dado lugar a un relanzamiento de la ética médica, enriquecida con nuevas formulaciones y argumentaciones, en los que la competencia profesional y los datos obtenidos de la evidencia científica se convierten en requisitos básicos para la toma de decisiones morales. Precisamente, esta confrontación, armonización de datos científicos y dilemas éticos distingue la nueva Bioética de la Clásica Deontología Médica enunciada por Hipócrates ya en el siglo V a.C.; surge, por tanto, esta nueva área de conocimiento y de discusión que parte de cómo una necesidad de logros, de acuerdos a nivel de la comunidad científica internacional pueden asegurar el respeto a la vida humana y a la dignidad personal en el ámbito de la investigación científica y el trabajo biomédico (17,18) .…”