RESUMEN
BACKGROUND: Primary brainstem hemorrhage (BSH) has the highest mortality and morbidity as a subtype of intracerebral hemorrhage. A major limitation of BSH research is the lack of a corresponding animal model. The purpose of this study was to establish a novel rat model of BSH and to characterize the resulting brain injury, especially focusing on white matter injury. METHODS: BSH was produced by stereotactically injecting autologous whole blood into the pons. Time course of hematoma resolution was observed by 7-T magnetic resonance imaging. White matter injury was evaluated in detail by multiple parameters including diffuse tensor imaging (DTI), demyelination, axonal injury, oligodendrocyte degeneration, and oligodendrocyte precursor cell proliferation. Brain water content and neurobehavior were also evaluated. RESULTS: Blood infusion (30 µL) led to a stable, reproducible hematoma in the right basotegmental pons. The hematoma absorption started, became obvious, and was nearly completed at 7, 14, and 30 days, respectively. Hematoma caused obvious brain edema at 3 days. White mater injury was observed pathologically, which was in line with decreased fractional anisotropy (FA) in DTI in the pons. FA reduction was also noticed in the cerebral peduncle and medulla. Behavioral abnormality persisted for at least 14 days and neurofunction was recovered within 1 month. CONCLUSIONS: This novel model can produce a stable hematoma resulting in brain edema, white matter injury, and neurofunctional deficits, which could be useful for future investigation of pathophysiological mechanisms and new treatment evaluation after BSH.
Asunto(s)
Conducta Animal , Transfusión de Sangre Autóloga , Edema Encefálico/etiología , Hematoma/etiología , Hemorragias Intracraneales/etiología , Leucoencefalopatías/etiología , Imagen por Resonancia Magnética , Puente/irrigación sanguínea , Sustancia Blanca/patología , Animales , Edema Encefálico/patología , Edema Encefálico/fisiopatología , Edema Encefálico/psicología , Imagen de Difusión Tensora , Modelos Animales de Enfermedad , Hematoma/patología , Hematoma/fisiopatología , Hematoma/psicología , Hemorragias Intracraneales/patología , Hemorragias Intracraneales/fisiopatología , Hemorragias Intracraneales/psicología , Leucoencefalopatías/patología , Leucoencefalopatías/fisiopatología , Leucoencefalopatías/psicología , Masculino , Puente/patología , Puente/fisiopatología , Ratas Sprague-Dawley , Factores de Tiempo , Sustancia Blanca/fisiopatologíaRESUMEN
The authors report the unusual case of a 58-year-old woman (MJP) suffering from left temporal throbbing headache, associated with confusion. Magnetic resonance imaging showed a 5 x 3 x 2 cm hematoma at the left posterior temporal--parietal junction (PTPJ). Repeated MRI of MJP's brain performed during a 4-month follow-up period showed decrease in hematoma size (2.3 x 1.5 x 1) with evidence for development of encephalomalacia and resorption of blood products involving the area of hemorrhage. MJP had mild transcortical sensory aphasia characterized by difficulty with reading and processing, with semantic paraphasic errors while speaking and some difficulty with repetition. MJP had remained normotensive and seizure free, on Vasotec therapy and Dilantin prophylaxis. An in vivo proton magnetic resonance spectroscopy (1H-MRS) performed during an 8-month follow-up period showed reduced concentration for N-acetyl aspartate (NAA) by 19.3% (F=4.09, P<0.04), and myo-inositol by 32.0% (F=5.16, P<0.02) in the left orbital frontal cortex (OFC) as compared with 16 healthy subjects (age- and sex-matched). Cognitive tests (the Wechsler abbreviated scale of intelligence (WASI) and the Stroop color--word interference) showed a significant impairment suggesting involvement of higher-order cognitive functioning (memory, learning, and general intelligence) and attentional system. The Spielberger state-trait anxiety inventory (STAI) showed increased anxiety at the moment of the current examination and decreased tendency to be anxious over a long period of time. The Beck Anxiety and Depression Inventory revealed minimal anxiety and mild to moderate levels of depression. It is hypothesized that the PTPJ hematoma triggered long-distance pathways linking PTPJ area and frontal lobe, including OFC, which resulted in abnormal chemical changes in the left OFC and in cognitive tests impairment, and in long-term anxiety state changes.