Mouse Intracerebral Hemorrhage Models Produce Different Degrees of Initial and Delayed Damage, Axonal Sprouting, and Recovery

Abstract

The mechanisms of delayed damage and recovery after intracerebral hemorrhage (ICH) remain poorly defined. Two rodent models of ICH are commonly used: injection of the enzyme collagenase (cICH) and injection of autologous blood (bICH). In mice, we compared the effects of these two models on initial and delayed tissue damage, motor system connections, and behavioral recovery. There is no difference in lesion size between models. Injection of autologous blood causes greater mass effect and early mortality. However, cICH produces greater edema, inflammation, and cell death. Injection of the enzyme collagenase causes greater loss of cortical connections and secondary shrinkage of the striatum. Intracerebral hemorrhage occurs within the motor system connections of the striatum. Mapping of the projections of the forelimb motor area shows a significant sprouting in motor cortex projections only in cICH. Both models of ICH produce deficits in forelimb motor control. Behavioral recovery occurs by 5 weeks in cICH and 9 weeks in bICH. In summary, cICH and bICH differ in almost every facet of initial and delayed stroke pathophysiology, with cICH producing greater initial and secondary tissue damage and greater motor system axonal sprouting than bICH. Motor recovery occurs in both models, suggesting that motor system axonal sprouting in cICH is not causally associated with recovery.

Electroacupunctre improves motor impairment via inhibition of microglia-mediated neuroinflammation in the sensorimotor cortex after ischemic stroke

“…It has been reported that activated microglia increased proinflammatory cytokines, including TNF-α, IL-1β and IL-6 in the ischemic stroke, which exacerbates the cortical selective neuronal loss and long-lasting sensorimotor behavior deficits [7][8]17,[55][56]. Long-term neuroinflammation is strongly induced gray-and white-matter damage, which contributes to long-term sensorimotor impairment [57].…”

Hydrogel-delivered brain-derived neurotrophic factor promotes tissue repair and recovery after stroke

“…Axonal connections were compared across hydrogel þ medBDNF, hydrogel þ highBDNF, direct delivery of soluble BDNF, and to hydrogel injection alone using linear fluorescent measurements which significantly correlate with axonal counts. 28 Hydrogel þ medBDNF induces significant axonal sprouting from peri-infarct motor cortex to contralateral striatum, as seen by increased axonal labeling within this projection compared with the control brain (Figure 3d and f). Stroke causes a loss of motor system connections within ipsilateral cortex to the infarct and in the projections of motor cortex to contralateral cortex and ipsilateral striatum (Figure 3a and c).…”

“…[3][4][5] Mice survived 1 week after tracer injection and tissue processed for densitometric analysis of axonal label in coronal tissue sections using fluorescence measurement methods. 28 In a separate study, mice in groups of control, stroke-alone, and stroke þ hydrogel þ medBDNF (n ¼ 5-6 per group) received the same stroke and BDA injection. After euthanasia, the tissue was processed for tangential sections through cortex using a quantitative cortical mapping procedure.…”

“…4,5 To determine the effect of hydrogel-delivered BDNF on axonal sprouting in periinfarct cortex, we densitometrically measured motor system axonal connections 28 after BDNF delivery in prominent axonal systems of the motor cortex: ipsilateral connections to adjacent cortical areas, to contralateral motor cortex, and to ipsilateral and contralateral striatum. The axonal tracer BDA was microinjected into forelimb motor cortex that is preserved, anterior to the stroke site, 4 weeks after BDNF delivery (5 weeks after stroke), a time period in which axonal sprouting is seen in this stroke model.…”

Intracerebral Hemorrhage as an Axonal Tract Injury Disorder with Inflammatory Reactions

“…11,12) Injection of autologous blood and injection of collagenase (to disrupt vascular walls) into the brain parenchyma are the representative procedures to produce pathology of ICH in rodent brains. In many studies the striatum (including the putamen) is used as the focal site of experimental ICH because this region is susceptible to ICH incidents in humans and is easily accessible by surgical manipulations.…”