Behavioral Tests After Intracerebral Hemorrhage in the Rat

Abstract

Background and Purpose-In humans, intracerebral hemorrhage (ICH) causes marked perihematomal edema formation and neurological deficits. A rat ICH model, involving infusion of autologous blood into the caudate, has been used extensively to study mechanisms of edema formation, but an examination of behavioral outcome would improve its preclinical utility and provide a more rigorous assessment of the pathological cascade of events over time. The purpose of this study was to use a battery of sensorimotor function tests to examine the neurological effects of ICH in the rat and to examine which components of the hematoma are involved in generating those effects. Methods-The behavioral tests used were forelimb placing, preference for forelimb use for weight shifts during vertical exploration of a cylindrical enclosure, and a corner turn test. Rats were tested from day 1 to day 28 after injection of autologous whole blood; injection of blood plus hirudin (thrombin inhibitor), packed red blood cells, thrombin, or saline; or needle placement only. Results-The battery of tests indicated that there were marked neurological deficits by day 1 after ICH, with progressive recovery of function over 4 weeks. The forelimb placing score paralleled changes in edema. Injection of thrombin caused and injection of hirudin reduced the ICH-induced neurological deficits. Injection of packed red blood cells, which causes delayed edema formation, induced delayed neurological deficits Conclusions-These tests allow continuous monitoring of neurological deficits after rat ICH and assessment of therapeutic interventions. The time course of the neurological deficit closely matched the time course of cerebral edema for both ICH and injection of blood components. There was marked recovery of function after ICH, which may be amenable to therapeutic manipulation.

Behavioral tests for preclinical intervention assessment

“…13,19,33 The test is well suited for testing both mice and rats. It is one of the only tests that can detect mild injury and chronically stable deficits in mice.…”

Skilled reaching impairments follow intrastriatal hemorrhagic stroke in rats

“…This and our previous study [22] illustrate that the choice of behavioral tests depends on the model of stroke, the location and severity of insult, the timing of testing, as well as practical limitations [22]. For the whole blood model, we recommend using the single pellet-reaching task with other simple, less time-consuming tasks (e.g., forelimb placing score) known to be sensitive to long-term deficits in this insult [17]. We expect that such a battery will improve preclinical studies and help to identify truly effective therapies.…”

“…The infusion of blood, rather than collagenase, better mimics the single large bleed that occurs in most ICH patients [15]. Using this ICH model, Hua et al [17] carefully identified a battery of tests sensitive to injury, tracked recovery over time, and examined the relationship between functional outcome and brain edema. Although each of their tests (corner turn test, forelimb use asymmetry (cylinder) test and forelimb placing test) detected ICH injury, marked recovery to pre-surgical levels occurred by 1 month in two of the tests.…”

Establishing A Model of Supratentorial Hemorrhage in the Piglet

“…The significant neurological impairment in our model has never been reported in pig model of ICH by others. Many neurologic impairment assessment methods had been described, including Zea Longa assessment of neurological deficits (Longa et al 1989), spontaneous ipsilateral circling test, contralateral hindlimb retracting test, beam walking test (Altumbabic et al 1998), forelimb placing test, forelimb asymmetry test, and corner turn test (Schallert et al 2000;Hua et al 2002), but whether these methods are suitable for piglet model of ICH remains unknown. After taking all these tests into consideration, we chose and modified Zea Longa's assessment, which was easily performed and could evaluate the accurate condition of neurological deficits of piglets.…”