Abstract
Spontaneous intracerebral hemorrhage (ICH) is one of the most lethal forms of stroke. From the limited previous studies and our preliminary data, white matter is considered a key predictor of the outcome and potential target of recovery. The traditional ICH model induced by injection of autologous blood or bacterial collagenase into striatum (ST) demonstrated a spontaneous functional recovery within one or 2 months. We hypothesis that an internal capsule (IC) lesion might lead to long-term axonal damage and long lasting functional deficits. Thus in this study, a modified internal capsule ICH model was conducted in rats, and the axonal damage, neurological deficits, histopathology as well as electrophysiology were characterized. The finding demonstrated that compared to ST group, the modified IC lesioned model exhibited a relatively smaller lesion volume with consistent axonal loss/degeneration and long-lasting neurological dysfunction at 2 months after ICH. Functionally, the impairment of the mNSS, ratio of contralateral forelimb usage, four limb stand index, contralateral duty cycle and ipsilateral SSEPs amplitude remained significant at 56 days. Structurally, the significant loss of PKCγ in ipsilateral cortical spinal tracts of IC group and the consistent axonal degeneration with several axonal retraction bulbs and enlarged tubular space was observed at 56 days after ICH. This study suggested that a modified IC lesioned model was proved to have long lasting neurological deficits. A comprehensive understanding of the dynamic progression after experimental ICH should aid further successful clinic translation in animal ICH studies, and provide new insights into the role of whiter matter injury in the mechanism and therapeutic targets of ICH.
Highlights
Spontaneous intracerebral hemorrhage (ICH) is the most lethal subtypes of stroke with a two times higher rate of incidence in Asian people, results in 30–50% mortality (Feigin et al, 2009) and only 10–20% of all survivors remaining independent after 6 months from onset
In the first month after ICH, tissue loss volume decreased in line with hematoma resolution (Matsushita et al, 2013)
In internal capsule (IC) lesioned model, the tissue loss volume increased in line with edema and the mass effect of the hematoma, and white matter degeneration, according to those results described in Masuda et al (2007a)
Summary
Spontaneous intracerebral hemorrhage (ICH) is the most lethal subtypes of stroke with a two times higher rate of incidence in Asian people, results in 30–50% mortality (Feigin et al, 2009) and only 10–20% of all survivors remaining independent after 6 months from onset (van Asch et al, 2010). To date, none of the preclinical research that proven positive results has successfully translated in clinical setting. This failure has occurred for several reasons that mainly in poor modeling, lack of behavioral testing and inadequate experimental design (Manaenko et al, 2011). The rodent ICH model induced by the injection of autologous blood or bacterial collagenase into the basal ganglia striatum (ST) has been widely used since the 1980s (Rosenberg et al, 1990) and served as the classical and reproducible ICH animal model in most preclinical studies (Nath et al, 1986; MacLellan et al, 2010; Rosenberg, 2011). The value of the different modified models remains controversial, the numerous studies and reviews have reached a consensus that an appropriate and reproducible model should be selected based on a specific study purpose and to achieve a more reliable clinical translation
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