Pharmacogenetic activation of parvalbumin interneurons in the prefrontal cortex rescues cognitive deficits induced by adolescent MK801 administration.

The cognitive symptoms of schizophrenia (SZ) present a significant clinical burden. They are treatment resistant and are the primary predictor of functional outcomes. Although the neural mechanisms underlying these deficits remain unclear, pathological GABAergic signaling likely plays an essential role. Perturbations with parvalbumin (PV)-expressing fast-spiking (FS) interneurons in the prefrontal cortex (PFC) are consistently found in post-mortem studies of patients with SZ, as well as in animal models. Our studies have shown decreased prefrontal synaptic inhibition and PV immunostaining, along with working memory and cognitive flexibility deficits in the MK801 model. To test the hypothesized association between PV cell perturbations and impaired cognition in SZ, we activated prefrontal PV cells by using an excitatory DREADD viral vector with a PV promoter to rescue the cognitive deficits induced by adolescent MK801 administration in female rats. We found that targeted pharmacogenetic upregulation of prefrontal PV interneuron activity can restore E/I balance and improve cognition in the MK801 model. Our findings support the hypothesis that the reduced PV cell activity levels disrupt GABA transmission, resulting in the disinhibition of excitatory pyramidal cells. This disinhibition leads to an elevated prefrontal excitation/inhibition (E/I) balance that could be causal for cognitive impairments. Our study provides novel insights into the causal role of PV cells in cognitive function and has clinical implications for understanding the pathophysiology and management of SZ.

Mycotic aneurysm presenting as subdural empyema: illustrative case.

BACKGROUND: Mycotic aneurysms (MAs) are rare intracranial pathologies. They are associated with spontaneous rupture, which is often the first presenting sign. Subarachnoid hemorrhage and intraparenchymal hemorrhage are the most common sequelae of ruptured MAs, with subdural hematoma being an atypical presentation. The presentation of an MA as a subdural empyema has not yet been reported in the literature. OBSERVATIONS: The authors discussed a 68-year-old man who presented with subdural empyema and received surgery for evacuation. He was found to have a ruptured mycotic aneurysm intraoperatively. LESSONS: This case demonstrated a rare and atypical presentation of an MA.

It's not always the shunt: Microthombi formation in venous collaterals causing symptoms of shunt failure in the setting of shunted hydrocephalus.

We present a patient with a history of shunted hydrocephalus due to neonatal iatrogenic thoracic venous occlusion with subsequent interval development of spontaneous thoracic venous collateral occlusion as a young adult presenting with symptoms of ventriculoperitoneal shunt failure. Though the patient's presenting symptoms were suggestive of shunt failure in the setting of known shunt dependent hydrocephalus, specific ophthalmologic findings, including venous engorgement, retinal and subconjunctival hemorrhages as well as periorbital edema in conjunction with papilledema, led to the correct diagnosis of cranio-orbital congestion secondary to microthrombi formation in the venous collateral anomalies of her chest wall. This pathology was successfully managed with warfarin.