Persistent Blunting of Penumbral Leukocyte Mobilization by Beta Blockade Administered for Two Weeks After Traumatic Brain Injury.
J Surg Res
; 280: 196-203, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-35994981
ABSTRACT
INTRODUCTION:
Beta-blockers (BB) after traumatic brain injury (TBI) accelerate cognitive recovery weeks after injury. BBs also inhibit leukocyte (LEU) mobilization to the penumbral blood brain barrier (BBB) 48-h after TBI. It is unclear whether the latter effects persist longer and accompany the persistent cognitive improvement. We hypothesized that 2 wk of BB after TBI reduce penumbral BBB leukocyte-endothelial interactions.METHODS:
Thirty CD1 mice underwent TBI (controlled cortical impact, CCI 6 m/s velocity, 1 mm depth, 3 mm diameter) or sham craniotomy followed by i.p. saline (NS) or propranolol (1, 2, 4 mg/kg) every 12 h for 14 d. On day 14, in vivo pial intravital microscopy visualized endothelial-LEU interactions and BBB microvascular leakage. Day 14 Garcia neurological test scores and animal weights were compared to preinjury levels reflecting concurrent clinical recovery.RESULTS:
LEU rolling was greatest in CCI + NS when compared to sham (P = 0.03). 4 mg/kg propranolol significantly reduced postCCI LEU rolling down to uninjured sham levels (P = 0.03). LEU adhesion and microvascular permeability were not impacted at this time interval. Untreated injured animals (CCI + NS) scored lower Garcia neurological test and greater weight loss recovery at day 14 when compared to preinjury (P < 0.05). Treatment with higher doses of propranolol (2, 4 mg/kg), improved weight loss recovery (P < 0.001).CONCLUSIONS:
LEU rolling alone, was influenced by BB therapy 14 d after TBI suggesting that certain penumbral neuroinflammatory cellular effects of BB therapy after TBI persist up to 2 wk after injury potentially explaining the pervasive beneficial effects of BBs on learning and memory.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Edema Encefálico
/
Lesões Encefálicas Traumáticas
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article