Changes in striatal dopamine neurohistochemistry and biochemistry after incomplete transient cerebral ischemia in the rat

Abstract

To evaluate the development of striatal ischemic cell damage in relation to alterations in dopamine (DA) transmission, one year old male Wistar rats underwent a 15 min incomplete cerebral ischemia (ICI) induced by occlusion of the common carotid arteries and by hypovolemic hypotension. The animals were divided into the following experimental groups: sham operated rats, rats with ICI without reperfusion, and rats with ICI followed by 60 min, 24 h, 72 h and 144 h of recirculation. The ischemia induced striatal lesions were investigated in serial coronal brain sections, stained with cresylviolet or immunostained for dopamine and cAMP regulated phosphoprotein (DARPP-32), for tyrosine hydroxylase (TH) and for glial fibrillary acidic protein (GFAP) immunoreactivities (IR). Measurements of striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels were made on analogous experimental groups using HPLC methods. Signs of degeneration in small to medium sized neurons were already seen after 60 min of postischemic reperfusion together with slight decreases of DARPP-32 IR and increases of GFAP IR. The damage continued to increase up to 144 h, and after 24 h of recirculation there were clearly defined areas of reduced DARPP-32 IR, overlapping with increased TH IR and increased GFAP IR. The levels of DA, DOPAC and HVA increased sharply after 60 min (151%, 462% and 201%, respectively) remained high after 24 h and normalized after 72 h of recirculation. The DA metabolism was high after 60 min and had already normalized after 24 h of recirculation. The increased DA metabolism in striatal nerve terminals in response to ischemic injury may reflect an early degenerative change in the DA terminals. The long-lasting increase in TH IR may to some extent represent an adaptive change in response to the disappearance of DA receptor-containing nerve cells. Based on the present findings it is possible that an increased D1 transmission in neostriatum immediately following the ischemic injury may contribute to striatal nerve cell degeneration in which an enhancement of NMDA receptor transduction may be implicated.

Frequent Episodes of Brief Ischemia Sensitize the Fetal Sheep Brain to Neuronal Loss and Induce Striatal Injury

“…Striatal neurons, particularly small-to medium-sized ones, have been shown to attain ischemic cell change more rapidly than cortical and hippocampal neurons (20). This early degeneration of small-to medium-sized striatal neurons has been related to changes in striatal dopamine neurohistochemistry (21). It may be that repeated insults enhance these early ischemic cell changes, sensitizing striatal neurons in particular.…”

Neuroprotective Effects of Salidroside on Cerebral Ischemia/Reperfusion-Induced Behavioral Impairment Involves the Dopaminergic System

“…These outcomes are in line with previous reports of enlarged granular TH terminals and large synaptophysin-positive dots after cerebral ischemia/reperfusion in the rat CPu (Sabogal et al, 2014). This phenomenon was considered as a compensatory function of the dopaminergic nerve terminals in response to the striatal neuron degeneration (Nemeth et al, 1991;Korematsu et al, 1993). An earlier study reported that salidroside upregulated the expression of dopamine transporter in the striatum in an animal model of a neurodegenerative disease (Li and Chen, 2019).…”