The cannabinoid type-1 receptor (CB1R) is one of the most abundant members of the G protein-coupled receptor family in the central nervous system. Once activated by their cognate ligands, endocannabinoids, CB1Rs generally limit the timing of neurotransmitter release at many cortical synapses. Prior studies have indicated the involvement of CB1R in neurodegeneration and in various neuronal insults, with an emphasis on their neuroprotective role. In the present study we used a novel selective CB1R radioligand to investigate regional variations in CB1R ligand binding as a factor of progressive Braak tau pathology in the frontal cortex of Alzheimer's disease (AD) patients. The frontal cortex was chosen for this study due to the high density of CB1Rs and their well-characterized involvement in the progression of AD. Post-mortem prefrontal cortex samples from AD patients from Braak stages I to VI and controls were subjected to CB1R autoradiography with [125I]SD-7015 as radioligand. Regional concentration of [125I]SD-7015, corresponding to, and thereby representing, regional CB1R densities, were expressed in fM/g_tissue. The results show that CB1R density inversely correlates with Braak tau pathology with the following tendency: controls
Cannabinoid type-1 receptors (CB1Rs) modulate synaptic neurotransmission by participating in retrograde signaling in the adult brain. Increasing evidence suggests that cannabinoids through CB1Rs play an important role in the regulation of motor activities in the striatum. In the present study, we used human brain samples to examine the relationship between CB1R and dopamine receptor density in case of Parkinson’s disease (PD).
Post mortem putamen, nucleus caudatus and medial frontal gyrus samples obtained from PD patients were used for CB1R and dopamine D2/D3 receptor autoradiography. [125I]SD7015, a novel selective CB1R inverse agonist, developed by a number of the present co-authors, and [3H]raclopride, a dopamine D2/D3 antagonist, were used as radioligands. Our results demonstrate unchanged CB1R density in the putamen and nucleus caudatus of deceased PD patients, treated with levodopa (l-DOPA). At the same time dopamine D2/D3 receptors displayed significantly decreased density levels in case of PD putamen (control: 47.97 ± 10.00 fmol/g, PD: 3.73 ± 0.07 fmol/g (mean ± SEM), p < 0.05) and nucleus caudatus (control: 30.26 ± 2.48 fmol/g, PD: 12.84 ± 5.49 fmol/g, p < 0.0005) samples. In contrast to the putamen and the nucleus caudatus, in the medial frontal gyrus neither receptor densities were affected.
Our data suggest the presence of an unaltered CB1R population even in late stages of levodopa treated PD. This further supports the presence of an intact CB1R population which, in line with the conclusion of earlier publications, may be utilized as a pharmacological target in the treatment of PD. Furthermore we found discrepancy between a maintained CB1R population and a decreased dopamine D2/D3 receptor population in PD striatum. The precise explanation of this conundrum requires further studies with simultaneous examination of the central cannabinoid and dopaminergic systems in PD using higher sample size.
Here we present a successful intra-arterial thrombolysis performed in the second trimester of pregnancy (21 weeks). The intervention resulted in complete recanalization of the occluded right middle cerebral artery and favourable clinical and gestational outcome. Together with cases described in respective medical literature our report affirms that in pregnancy acute ischemic stroke could be treated effectively applying intra-arterial thrombolysis (using rt-PA). This therapy could provide opportunity to help in such desperate situations.
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