Forebrain Ischemia Triggers GABAergic System Degeneration in Substantia Nigra at Chronic Stages in Rats

Abstract

The long-term consequences of forebrain ischemia include delayed Parkinson's syndrome. This study revealed delayed neurodegeneration in the substantia nigra 8 weeks after 12.5 minutes of global ischemia in rat brain. Following neuronal loss of 30–40% in central and dorsolateral striatum at day 3, neuronal damage in the substantia nigra (SN) was assessed at 4–8 weeks using immunohistochemistry for glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), and calretinin (CR). At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)—significantly decreased. CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01). Movement coordination was impaired at day 56, as evaluated using beam-walking test (time-to-traverse 5.6 ± 1.2 sec versus 11.8 ± 5.4 sec; sham versus ischemia, p < .05, n = 5, and 7, resp.). Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.

Huatuo Zaizao pill promotes functional recovery and neurogenesis after cerebral ischemia-reperfusion in rats

“…Forelimb asymmetry was then calculated using the formula: 100 × (ipsilateral forelimb use + 1/2 both)/total forelimb use. A beam-walking test was applied to assess coordination and integration of motor movements as a measure of functional recovery in I/R-injured rats [20]. Rats were trained for 2 days before I/R injury.…”

Global Cerebral Ischemia: Synaptic and Cognitive Dysfunction

“…In animals, motor function is commonly assessed using a few different techniques examining balance, coordination, and activity [207-210]. Locomotor function is frequently examined in rats using the beam walking task [208]. This test consists of an animal walking a narrow beam to escape an aversive stimulus, scoring the number of foot faults and amount of time it takes to cross the beam Fig.…”

“…(4C). Global cerebral ischemia increases the amount of time required to complete this task, suggesting a deficit in motor function [207, 208]. The open field test is used to test overall activity in rodents [210], where an animal is placed into a square or circular arena (for anywhere between 5 and 30 minutes) and allowed to move freely.…”

Limbic system pathologies associated with deficiencies and excesses of the trace elements iron, zinc, copper, and selenium

“…The main structures forming the limbic system (Figure 1) are divided into two regions: the cortical regions, including the parahippocampal and cingulate gyri, the prefrontal cortex, and the orbitofrontal cortex; and the subcortical regions, comprising the hippocampus, the amygdaline nucleus, the septal nucleus, the nucleus accumbens, the striatum, the mammillary bodies, the hypothalamus, the thalamus, the ventral tegmental area, the raphe nucleus, the locus coeruleus, and the substantia nigra 28,29 Table 1. presents the main functions of the limbic system structures, based on several literature reviews 26,29–34 …”