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Intravenous Administration of Anti-CD47 Antibody Augments Hematoma Clearance, Mitigates Acute Neuropathology, and Improves Cognitive Function in a Rat Model of Penetrating Traumatic Brain Injury.
Wang, Ping; Yang, Xiaofang; Yang, Fangzhou; Cardiff, Katherine; Houchins, Melonie; Carballo, Noemy; Shear, Deborah A; Scultetus, Anke H; Bailey, Zachary S.
Afiliación
  • Wang P; Brain Trauma Neuroprotection, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
  • Yang X; Brain Trauma Neuroprotection, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
  • Yang F; Brain Trauma Neuroprotection, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
  • Cardiff K; Brain Trauma Neuroprotection, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
  • Houchins M; Brain Trauma Neuroprotection, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
  • Carballo N; Brain Trauma Neuroprotection, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
  • Shear DA; Brain Trauma Neuroprotection, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
  • Scultetus AH; Brain Trauma Neuroprotection, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
  • Bailey ZS; Brain Trauma Neuroprotection, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
J Neurotrauma ; 2024 Jul 03.
Article en En | MEDLINE | ID: mdl-38874230
ABSTRACT
Traumatic brain injury (TBI)-induced intracerebral hematoma is a major driver of secondary injury pathology such as neuroinflammation, cerebral edema, neurotoxicity, and blood-brain barrier dysfunction, which contribute to neuronal loss, motor deficits, and cognitive impairment. Cluster of differentiation 47 (CD47) is an antiphagocytic cell surface protein inhibiting hematoma clearance. This study was designed to evaluate the safety and efficacy of blockade of CD47 via intravenous (i.v.) administration of anti-CD47 antibodies following penetrating ballistic-like brain injury (PBBI) with significant traumatic intracerebral hemorrhage (tICH). The pharmacokinetic (PK) profile of the anti-CD47 antibody elicited that antibody concentration decayed over 7 days post-administration. Blood tests and necropsy analysis indicated no severe adverse events following treatment. Cerebral hemoglobin levels were significantly increased after injury, however, anti-CD47 antibody administration at 0.1 mg/kg resulted in a significant reduction in cerebral hemoglobin levels at 72 h post-administration, indicating augmentation of hematoma clearance. Immunohistochemistry assessment of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (IBA1) demonstrated a significant reduction of GFAP levels in the lesion core and peri-lesional area. Based on these analyses, the optimal dose was identified as 0.1 mg/kg. Lesion volume showed a reduction following treatment. Rotarod testing revealed significant motor deficits in all injured groups but no significant therapeutic benefits. Spatial learning performance revealed significant deficits in all injured groups, which were significantly improved by the last testing day. Anti-CD47 antibody treated rats showed significantly improved attention deficits, but not retention scores. These results provide preliminary evidence that blockade of CD47 using i.v. administration of anti-CD47 antibodies may serve as a potential therapeutic for TBI with ICH.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Neurotrauma Asunto de la revista: NEUROLOGIA / TRAUMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Neurotrauma Asunto de la revista: NEUROLOGIA / TRAUMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos