Longitudinal imaging of the availability of dopamine transporter and D2 receptor in rat striatum following mild ischemia

Abstract

The changes in the availability of striatal dopamine transporter and dopamine D2 receptor after mild focal ischemia in rats were measured using a small animal positron emission tomography system. Mild focal ischemia was induced by 20-minute middle cerebral artery occlusion. [11 C]PE2I binding to dopamine transporter was transiently increased on the ipsilateral side of the striatum at 2 days after middle cerebral artery occlusion. On day 7 and 14 after middle cerebral artery occlusion, [11 C]PE2I binding levels were decreased. In contrast, [ 11 C]raclopride binding to dopamine D2 receptor in the ipsilateral striatum had not changed at 2 days after middle cerebral artery occlusion. [11 C]Raclopride binding was significantly decreased on the ischemic side of the striatum at 7 and 14 days after middle cerebral artery occlusion. Moreover, on day 1 and 2 after middle cerebral artery occlusion, significant circling behavior to the contralateral direction was induced by amphetamine challenge. This behavior disappeared at 7 days after middle cerebral artery occlusion. At 14 days, circling behavior to the ipsilateral direction (middle cerebral artery occlusion side) was significantly increased, and that to the contralateral direction also appeared again. The present study suggested that amphetamineinduced circling behavior indicated striatal dopaminergic alterations and that dopamine transporter and dopamine D2 receptor binding could be key markers for predicting motor dysfunction after mild focal ischemia.

Cardiovascular factors are related to dopamine integrity and cognition in aging

“…Even though we cannot infer the temporal order of events due to the cross‐sectional nature of this study, previous work suggests that reduced cerebrovascular integrity reduces DA‐system integrity. For instance, in a longitudinal animal study, induction of cerebral ischemia in rats led to reduced striatal 11 C‐raclopride binding over time . Another study showed that heart failure was followed by attenuated cerebral blood flow as well as DA levels …”

Detection of neuroinflammation before selective neuronal loss appearance after mild focal ischemia using [18F]DPA-714 imaging

“…The MCAO rat model was established as in our previous studies [ 14 ], with some modifications. Briefly, rats weighing approximately 300 g were initially anesthetized with 5% isoflurane and maintained under anesthesia with 2% isoflurane (room air, 1.5 L/min).…”

“…Further, striatal selective neuronal loss (SNL) can be induced by brief MCAO without infarction, but this includes microglia and astrocyte activation [ 12 , 13 ]. In previous studies, we reported SNL at 7 days after 20-min MCAO, without acute brain infarction [ 14 ]. Taken together, these lines of evidence suggest that the activation of microglia and astrocytes after mild ischemia might be a key factor in SNL.…”

Oophorectomy Reduces Estradiol Levels and Long-Term Spontaneous Neurovascular Recovery in a Female Rat Model of Focal Ischemic Stroke

“…In the sole report describing the effect of Ovx on neuronal function in the acute stage of ischemia, Pelligrino et al (1998) observed larger reduction in neuronal power within the first 30 min following common carotid artery clamping combined with hemorrhagic hypotension in Ovx female rats compared to Sham animals. However, early neuronal dysfunction is not a reliable predictor of long term injury ( Moore et al, 2000 ; Lake et al, 2017 ; Momosaki et al, 2017 ). To develop novel therapeutic approaches, it is necessary to have a model that recapitulates the combined effect of estrogen loss and the sequelae of events following ischemia.…”