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Blood brain barrier is impermeable to solutes and permeable to water after experimental pediatric cardiac arrest
Erika E Tress1, Robert S B Clark2, Lesley M Foley3
1University of Pittsburgh, Department of Pediatrics, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Insights
In pediatric cardiac arrest survivors, the blood-brain barrier (BBB) remains impermeable to tested substances, hindering neuroprotective therapy development. Early brain edema occurs despite this BBB integrity.
Area of Science:
- Neuroscience
- Pediatric Critical Care
- Pharmacology
Background:
- Pediatric cardiac arrest (CA) frequently leads to poor neurological outcomes.
- Effective neuroprotective therapies require understanding blood-brain barrier (BBB) permeability to medications.
- The BBB's role in pediatric CA neurological injury is not fully understood.
Purpose of the Study:
- To investigate BBB permeability to small and large molecules after pediatric asphyxial CA.
- To assess changes in brain water content following pediatric asphyxial CA.
Main Methods:
- Induction of 9-minute asphyxial CA in juvenile rats (16-18 days old).
- Assessment of BBB permeability to sodium fluorescein, gadoteridol (small molecules), and immunoglobulin G (large molecule) at 1, 4, and 24 hours post-resuscitation.
- Measurement of percent brain water using wet-to-dry brain weight.
Main Results:
- No significant difference in BBB permeability to tested tracers between asphyxial CA and sham groups over 24 hours.
- Increased cerebral water content (brain edema) observed at 3 hours post-CA compared to shams.
- BBB integrity is maintained despite early signs of brain edema after pediatric asphyxial CA.
Conclusions:
- Nine minutes of asphyxial CA does not compromise BBB permeability to conventional small or large molecule tracers within 24 hours.
- Early brain edema develops after pediatric CA, indicating potential for neurological damage.
- Future neuroprotective therapies for pediatric CA must demonstrate BBB penetration capabilities.
Abstract:
Pediatric asphyxial cardiac arrest (CA) results in unfavorable neurological outcome in most survivors. Development of neuroprotective therapies is contingent upon understanding the permeability of intravenously delivered medications through the blood brain barrier (BBB). In a model of pediatric CA we sought to characterize BBB permeability to small and large molecular weight substances. Additionally, we measured the percent brain water after CA. Asphyxia of 9 min was induced in 16-18 day-old rats. The rats were resuscitated and the BBB permeability to small (sodium fluorescein and gadoteridol) and large (immunoglobulin G, IgG) molecules was assessed at 1, 4, and 24 h after asphyxial CA or sham surgery. Percent brain water was measured post-CA and in shams using wet-to-dry brain weight. Fluorescence, gadoteridol uptake, or IgG staining at 1, 4h and over the entire 24 h post-CA did not differ from shams, suggesting absence of BBB permeability to these solutes. Cerebral water content was increased at 3h post-CA vs. sham. In conclusion, after 9 min of asphyxial CA there is no BBB permeability over 24h to conventional small or large molecule tracers despite the fact that cerebral water content is increased early post-CA indicating the development of brain edema. Evaluation of novel therapies targeting neuronal death after pediatric CA should include their capacity to cross the BBB.
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