ABSTRACT
Promoting hematoma absorption is a novel therapeutic strategy for intracerebral hemorrhage (ICH); however, the mechanism of hematoma absorption is unclear. The present study explored the function and potential mechanism of CD36 in hematoma absorption using in vitro and in vivo ICH models. Hematoma absorption in CD36-deficient ICH patients was examined. Compared with patients with normal CD36 expression, CD36-deficient ICH patients had slower hematoma adsorption and aggravated neurologic deficits. CD36 expression in perihematomal tissues in wild-type mice following ICH was increased, whereas the hematoma absorption in CD36(-/-) mice was decreased. CD36(-/-) mice also showed aggravated neurologic deficits and increased TNF-α and IL-1ß expression levels. The phagocytic capacity of CD36(-/-) microglia for RBCs was also decreased. Additionally, the CD36 expression in the perihematoma area after ICH in TLR4(-/-) and MyD88(-/-) mice was significantly increased, and hematoma absorption was significantly promoted, which was significantly inhibited by an anti-CD36 Ab. In vitro, TNF-α and IL-1ß significantly inhibited the microglia expression of CD36 and reduced the microglia phagocytosis of RBCs. Finally, the TLR4 inhibitor TAK-242 upregulated CD36 expression in microglia, promoted hematoma absorption, increased catalase expression, and decreased the H2O2 content. These results suggested that CD36 mediated hematoma absorption after ICH, and TLR4 signaling inhibited CD36 expression to slow hematoma absorption. TLR4 inhibition could promote hematoma absorption and significantly improve neurologic deficits following ICH.
Subject(s)
Blood Platelet Disorders/immunology , Brain Hemorrhage, Traumatic/immunology , CD36 Antigens/immunology , Genetic Diseases, Inborn/immunology , Hematoma, Epidural, Cranial/immunology , Nerve Tissue Proteins/immunology , Signal Transduction/immunology , Toll-Like Receptor 4/immunology , Adult , Aged , Animals , Blood Platelet Disorders/genetics , Blood Platelet Disorders/pathology , Brain Hemorrhage, Traumatic/genetics , Brain Hemorrhage, Traumatic/pathology , CD36 Antigens/genetics , Catalase/genetics , Catalase/immunology , Female , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/pathology , Hematoma, Epidural, Cranial/genetics , Hematoma, Epidural, Cranial/pathology , Humans , Hydrogen Peroxide/immunology , Male , Mice, Knockout , Microglia/immunology , Microglia/pathology , Middle Aged , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/immunology , Nerve Tissue Proteins/genetics , Phagocytosis/genetics , Phagocytosis/immunology , Retrospective Studies , Signal Transduction/genetics , Toll-Like Receptor 4/geneticsABSTRACT
We report on a 27-year-old male Caucasian with severe haemophilia A who presented with acute onset of neck pain with cervical nerve root irritation, due to a spinal epidural haematoma. His past medical history revealed carrying of a moderate weight as a possible traumatic mechanism. Under immediate factor VIII replacement therapy complete remission of the symptoms was achieved within several days. The diagnosis of spinal epidural haematoma and complete resorption was revealed by initial and follow-up magnetic resonance imaging studies of the cervical spine. Having reviewed the literature on spinal epidural haematoma, we present an overview of the treatment and outcome as regards haemophilia.
Subject(s)
HIV Seropositivity , Hematoma, Epidural, Cranial/immunology , Hemophilia A/immunology , Spinal Diseases/immunology , Adult , Hematoma, Epidural, Cranial/diagnosis , Humans , Magnetic Resonance Imaging , Male , Neck/innervation , Spinal Diseases/diagnosis , Spinal Nerve Roots/pathology , SyndromeABSTRACT
The case reported exemplifies a clinical picture markedly at variance with the chronology of symptoms and laboratory findings generally held to be typical in patients with post-traumatic shock. During a protracted clinical course this young man with a skull fracture and epidural haematoma experienced profound hypotension and adult respiratory distress syndrome (ARDS) well in advance of marked fourfold rise of circulating peripheral C3a desArg anaphylatoxin levels. This raises a note of caution with regard to diagnostic and/or therapeutic decisions based on anaphylatoxin assessment of neurosurgical trauma patients at risk of ARDS.
