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1.
J Cereb Blood Flow Metab ; 42(12): 2255-2269, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35854408

RESUMO

Epinephrine is the principal resuscitation therapy for pediatric cardiac arrest (CA). Clinical data suggest that although epinephrine increases the rate of resuscitation, it fails to improve neurological outcome, possibly secondary to reductions in microvascular flow. We characterized the effect of epinephrine vs. placebo administered at resuscitation from pediatric asphyxial CA on microvascular and macrovascular cortical perfusion assessed using in vivo multiphoton microscopy and laser speckle flowmetry, respectively, and on brain tissue oxygenation (PbO2), behavioral outcomes, and neuropathology in 16-18-day-old rats. Epinephrine-treated rats had a more rapid return of spontaneous circulation and brisk immediate cortical reperfusion during 1-3 min post-CA vs. placebo. However, at the microvascular level, epinephrine-treated rats had penetrating arteriole constriction and increases in both capillary stalling (no-reflow) and cortical capillary transit time 30-60 min post-CA vs. placebo. Placebo-treated rats had increased capillary diameters post-CA. The cortex was hypoxic post-CA in both groups. Epinephrine treatment worsened reference memory performance vs. shams. Hippocampal neuron counts did not differ between groups. Resuscitation with epinephrine enhanced immediate reperfusion but produced microvascular alterations during the first hour post-resuscitation, characterized by vasoconstriction, capillary stasis, prolonged cortical transit time, and absence of compensatory cortical vasodilation. Targeted therapies mitigating the deleterious microvascular effects of epinephrine are needed.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Animais , Ratos , Microscopia , Circulação Cerebrovascular/fisiologia , Parada Cardíaca/tratamento farmacológico , Parada Cardíaca/complicações , Epinefrina/farmacologia , Epinefrina/uso terapêutico , Ressuscitação
2.
J Neurotrauma ; 38(18): 2610-2621, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-33957773

RESUMO

Traumatic brain injury (TBI) alters microbial populations present in the gut, which may impact healing and tissue recovery. However, the duration and impact of these changes on outcome from TBI are unknown. Short-chain fatty acids (SCFAs), produced by bacterial fermentation of dietary fiber, are important signaling molecules in the microbiota gut-brain axis. We hypothesized that TBI would lead to a sustained reduction in SCFA producing bacteria, fecal SCFAs concentration, and administration of soluble SCFAs would improve functional outcome after TBI. Adult mice (n = 10) had the controlled cortical impact (CCI) model of TBI performed (6 m/sec, 2-mm depth, 50-msec dwell). Stool samples were collected serially until 28 days after CCI and analyzed for SCFA concentration by high-performance liquid chromatography-mass spectrometry/mass spectrometry and microbiome analyzed by 16S gene sequencing. In a separate experiment, mice (n = 10/group) were randomized 2 weeks before CCI to standard drinking water or water supplemented with the SCFAs acetate (67.5 mM), propionate (25.9 mM), and butyrate (40 mM). Morris water maze performance was assessed on post-injury Days 14-19. Alpha diversity remained stable until 72 h, at which point a decline in diversity was observed without recovery out to 28 days. The taxonomic composition of post-TBI fecal samples demonstrated depletion of bacteria from Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae families, and enrichment of bacteria from the Verrucomicrobiaceae family. Analysis from paired fecal samples revealed a reduction in total SCFAs at 24 h and 28 days after TBI. Acetate, the most abundant SCFA detected in the fecal samples, was reduced at 7 days and 28 days after TBI. SCFA administration improved spatial learning after TBI versus standard drinking water. In conclusion, TBI is associated with reduced richness and diversity of commensal microbiota in the gut and a reduction in SCFAs detected in stool. Supplementation of soluble SCFAs improves spatial learning after TBI.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/psicologia , Disbiose/etiologia , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/psicologia , Animais , Lesões Encefálicas Traumáticas/metabolismo , Eixo Encéfalo-Intestino , Suplementos Nutricionais , Ácidos Graxos Voláteis/química , Ácidos Graxos Voláteis/farmacologia , Fezes/microbiologia , Microbioma Gastrointestinal , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Doenças do Sistema Nervoso/metabolismo , Desempenho Psicomotor/efeitos dos fármacos , RNA Ribossômico 16S/genética , Resultado do Tratamento
3.
Exp Neurol ; 335: 113522, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152354

RESUMO

Pediatric asphyxial cardiac arrest (ACA) often leaves children with physical, cognitive, and emotional disabilities that affect overall quality of life, yet rehabilitation is neither routinely nor systematically provided. Environmental enrichment (EE) is considered a preclinical model of neurorehabilitation and thus we sought to investigate its efficacy in our established model of pediatric ACA. Male Sprague-Dawley rat pups (post-natal day 16-18) were randomly assigned to ACA (9.5 min) or Sham injury. After resuscitation, the rats were assigned to 21 days of EE or standard (STD) housing during which time motor, cognitive, and anxiety-like (i.e., affective) outcomes were assessed. Hippocampal CA1 cells were quantified on post-operative day-22. Both ACA + STD and ACA + EE performed worse on beam-balance vs. Sham controls (p < 0.05) and did not differ from one another overall (p > 0.05); however, a single day analysis on the last day of testing revealed that the ACA + EE group performed better than the ACA + STD group (p < 0.05) and did not differ from the Sham controls (p > 0.05). Both Sham groups performed better than ACA + STD (p < 0.05) but did not differ from ACA + EE (p > 0.05) in the open field test. Spatial learning and declarative memory were improved and CA1 neuronal loss was attenuated in the ACA + EE vs. ACA + STD group (p < 0.05). Collectively, the data suggest that providing rehabilitation after pediatric ACA can reduce histopathology and improve motor and cognitive ability.


Assuntos
Asfixia Neonatal/psicologia , Asfixia Neonatal/reabilitação , Cognição , Meio Ambiente , Parada Cardíaca/psicologia , Parada Cardíaca/reabilitação , Reabilitação Neurológica/métodos , Animais , Animais Recém-Nascidos , Ansiedade/etiologia , Ansiedade/psicologia , Asfixia Neonatal/patologia , Região CA1 Hipocampal/patologia , Parada Cardíaca/patologia , Masculino , Memória , Desempenho Psicomotor , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Aprendizagem Espacial
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