Activation of nucleus accumbens projections to the ventral tegmental area alters molecular signaling and neurotransmission in the reward system.

The nucleus accumbens (NAc) and the ventral tegmental area (VTA) are integral brain regions involved in reward processing and motivation, including responses to drugs of abuse. Previously, we have demonstrated that activation of NAc-VTA afferents during the acquisition of cocaine conditioned place preference (CPP) reduces the rewarding properties of cocaine and diminished the activity of VTA dopamine neurons. In the current study, we examined the impact of enhancing these inhibitory inputs on molecular changes and neurotransmission associated with cocaine exposure. Our results unveiled significant reductions in extracellular signal-regulated kinase (ERK) levels in the VTA and medial prefrontal cortex (mPFC) of both cocaine-treated groups compared with the saline control group. Furthermore, optic stimulation of NAc-VTA inputs during cocaine exposure decreased the expression of GluA1 subunit of AMPA receptor in the VTA and mPFC. Notably, in the NAc, cocaine exposure paired with optic stimulation increased ERK levels and reduced GluA1 phosphorylation at Ser845 as compared with all other groups. Additionally, both cocaine-treated groups exhibited decreased levels of GluA1 phosphorylation at Ser831 in the NAc compared with the saline control group. Moreover, cocaine exposure led to reduced ERK, GluA1, and GluA1 phosphorylation at Ser845 and Ser831 in the mPFC. Augmentation of GABAergic tone from the NAc during cocaine conditioning mitigated changes in GluA1 phosphorylation at Ser845 in the mPFC but reduced ERK, GluA1, and GluA1 phosphorylation at Ser831 compared with the saline control group. Interestingly, enhancing GABAergic tone during saline conditioning decreased GluA1 phosphorylation at Ser831 compared with the saline control group in the mPFC. Our findings highlight the influence of modulating inhibitory inputs from the NAc to the VTA on molecular signaling and glutamatergic neurotransmission in cocaine-exposed animals. Activation of these inhibitory inputs during cocaine conditioning induced alterations in key signaling molecules and AMPA receptor, providing valuable insights into the neurobiological mechanisms underlying cocaine reward and cocaine use disorder. Further exploration of these pathways may offer potential therapeutic targets for the treatment of substance use disorder.

Endovascular thrombectomy for acute ischemic stroke in Saudi Arabia: A single-center experience.

PURPOSE: This study aimed to investigate the outcomes of endovascular thrombectomy-treated patients in King Fahad Medical City, Riyadh, Saudi Arabia. METHODS: A retrospective cohort study of acute ischemic stroke patients treated with endovascular thrombectomy. Patients were included in the study between January 2015 and December 2022. Good outcomes were defined as a modified Rankin Scale (mRS) of 0-2 at 90 days. Multivariate logistic regression analysis was performed to identify the independent factors associated with good outcomes. RESULTS: During the study period, 369 patients with acute ischemic stroke (mean ± SD age, 61/- 15.1 yrs; 55.4 % male) underwent mechanical thrombectomy. Median National Institute of Health Stroke Scale (NIHSS) 15. Intravenous thrombolysis was administered to 34.5 % of the patients. Successful recanalization in the anterior circulation was achieved in 84.8 % of patients. Data from mRS performed after 90 days in the anterior circulation were available for 71.2 % of the patients. Of these, 41 % showed a good outcome, and the mortality rate was 22.4 %. The significant factors associated with good outcomes were age, NIHSS score, Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and short arterial puncture to recanalization. CONCLUSION: The number of patients who underwent endovascular thrombectomy has increased over time. The treatment outcomes and mortality were comparable with those of previous endovascular thrombectomy registries despite the high prevalence of DM, lower ASPECT score, and prolonged onset-to-recanalization time.

GABAergic projections to the ventral tegmental area govern cocaine-conditioned reward.

Elevated dopamine (DA) levels in the reward system underlie various drug-related behaviors, including addiction. As a major DA source in the reward system, the ventral tegmental area (VTA) is highly regulated by GABAergic inputs projected from different brain regions. It was previously shown that cocaine exposure reduces GABAA -mediated inhibitory postsynaptic currents (IPSCs) in VTA DA neurons; however, the specific GABAergic input underlying this inhibitory effect remains unknown. Here, using optogenetics, we separately activate and characterize different GABAergic afferents innervating the VTA, focusing on the rostromedial tegmental nucleus (RMTg) and the nucleus accumbens (NAc). GABAA -mediated IPSCs were recorded from VTA DA neurons, and the effect of DA-induced inhibition was measured in an afferent-specific manner. In addition, to examine the effect of enhanced GABAergic tone on the rewarding properties of cocaine, we exogenously activated the different GABAergic inputs during the acquisition phase of cocaine conditioned place preference (CPP). We found that acute cocaine exposure strongly attenuates GABAA -mediated IPSCs in VTA DA neurons from both inhibitory sources. Furthermore, exogenous light activation of both RMTg and NAc afferents in the VTA during the acquisition of cocaine-CPP significantly reduced the rewarding properties of cocaine. This behavioral observation was correlated with the reduction in the neuronal activity of VTA DA neurons as measured by the expression of c-fos. Together, these results emphasize the critical role of these GABAergic inputs to the VTA in modulating and potentially interrupting cocaine reward.

Safety of tissue plasminogen activator factor in an acute stroke patient with two unruptured cerebral aneurysms.

It is estimated that 6.6%-9.3% of stroke patients have unruptured cerebral aneurysms. The safety of recombinant tissue plasminogen activator (r-tPA) for stroke patients with these aneurysms is uncertain. We report the case of a 58-year old male presented with an acute ischemic stroke within 2 hours of symptom onset and was treated with r-tPA. Further investigation showed that the patient had 2 unruptured cerebral aneurysms. He recovered completely from the stroke and was discharged home in a few days with no deficits. Although cerebral aneurysms are considered a relative contraindication for r-tPA, our case provides evidence that it can be safely administered to these patients.

Supernatural Explanations of Neurological and Psychiatric Disorders Among Health Care Professionals at an Academic Tertiary Care Hospital in Saudi Arabia.

Saudi society is one of many where supernatural explanations for neurological and psychiatric disorders are prevalent among lay persons. The frequency of such beliefs among health care professionals in this country, however, is unknown. The frequency of supernatural explanations for neurological and psychiatric disorders was assessed in 126 health care professionals at an academic medical center in Jeddah. A high frequency of belief in supernatural factors as a cause for neurological and psychiatric illness, including the evil eye, divine testing and punishment, and sorcery, was found. Younger age and more junior level of training were associated with a higher likelihood of belief in supernatural causation. A surprisingly high prevalence of supernatural explanations was found among these health care professionals, 80% of whom were attending physicians or physicians in training. Future studies should focus on the potential impact of these beliefs on clinical practice.