Single-Cell Analysis in Cerebrovascular Research: Primed for Breakthroughs and Clinical Impact.

Data generated using single-cell RNA-sequencing has the potential to transform understanding of the cerebral circulation and advance clinical care. However, the high volume of data, sometimes generated and presented without proper pathophysiological context, can be difficult to interpret and integrate into current understanding of the cerebral circulation and its disorders. Furthermore, heterogeneity in the representation of brain regions and vascular segments makes it difficult to compare results across studies.

Early changes in spatiotemporal dynamics of remapped circuits and global networks predict functional recovery after stroke in mice.

Significance: Stroke is the leading cause of chronic disability in the United States. How stroke size affects post-stroke repair and recovery is poorly understood.

Aim: We aim to investigate the effects of stroke size on early repair patterns and determine how early changes in neuronal circuits and networks predict functional outcomes after stroke.

Normal aging in mice is associated with a global reduction in cortical spectral power and network-specific declines in functional connectivity.

Normal aging is associated with a variety of neurologic changes including declines in cognition, memory, and motor activity. These declines correlate with neuronal changes in synaptic structure and function. Degradation of brain network activity and connectivity represents a likely mediator of age-related functional deterioration resulting from these neuronal changes.

Clinical Problem-Solving: Fever and Rapidly Progressive Weakness in an Immunocompromised Patient.

Here we report the challenging case of a 41-year-old man with HIV complicated by AIDS and a history of prior neurologic injury from progressive multifocal leukoencephalopathy who presented with headache, fevers, lower extremity weakness, hyperreflexic upper extremities, and diminished lower extremity reflexes. We review the clinical decision-making and differential diagnosis for this presentation as the physical examination evolved and diagnostic testing changed over time.

HCN Channel Modulation of Synaptic Integration in GABAergic Interneurons in Malformed Rat Neocortex.

Cortical malformations are often associated with pharmaco-resistant epilepsy. Alterations in hyperpolarization-activated, cyclic nucleotide-gated, non-specific cation (HCN) channels have been shown to contribute to malformation associated hyperexcitability. We have recently demonstrated that expression of HCN channels and current amplitudes are reduced in layer (L) 5 pyramidal neurons of rats with freeze lesion induced malformations.

Regulation of epileptiform discharges in rat neocortex by HCN channels.

Hyperpolarization-activated, cyclic nucleotide-gated, nonspecific cation (HCN) channels have a well-characterized role in regulation of cellular excitability and network activity. The role of these channels in control of epileptiform discharges is less thoroughly understood. This is especially pertinent given the altered HCN channel expression in epilepsy.

Decreased hyperpolarization-activated currents in layer 5 pyramidal neurons enhances excitability in focal cortical dysplasia.

Focal cortical dysplasia is associated with the development of seizures in children and is present in up to 40% of intractable childhood epilepsies. Transcortical freeze lesions in newborn rats reproduce many of the anatomical and physiological characteristics of human cortical dysplasia. Rats with freeze lesions have increased seizure susceptibility and a region of hyperexcitable cortex adjacent to the lesion.

A novel animal model to study hot flashes: no effect of gonadotropin-releasing hormone.

Objective: Menopausal hot flashes compromise the quality of life for most women. The physiological mechanisms underlying hot flashes remain poorly understood, and the absence of an animal model to investigate hot flashes hinders investigations in this field.

Methods: We first developed the sheep as a model to study peripheral skin temperature changes using fever-inducing lipopolysaccharide (LPS; 200 microg/kg) administered to ovary-intact ewes.

Dendritic spine pathologies in hippocampal pyramidal neurons from Rett syndrome brain and after expression of Rett-associated MECP2 mutations.

Rett syndrome (RTT) is an X chromosome-linked neurodevelopmental disorder associated with the characteristic neuropathology of dendritic spines common in diseases presenting with mental retardation (MR). Here, we present the first quantitative analyses of dendritic spine density in postmortem brain tissue from female RTT individuals, which revealed that hippocampal CA1 pyramidal neurons have lower spine density than age-matched non-MR female control individuals. The majority of RTT individuals carry mutations in MECP2, the gene coding for a methylated DNA-binding transcriptional regulator.

The gonadotropin-releasing hormone type I receptor is expressed in the mouse cerebellum.

Gonadotropin-releasing hormone (GnRH) is a decapeptide hypothalamic hormone that was named according to its first discovered function--at the head of the neuroendocrine reproductive axis. Numerous other organ systems express GnRH and/or its receptor, although a specific physiological role for GnRH outside of the reproductive axis has yet to be established. Several studies in lower vertebrates have reported GnRH and/or its receptor in the cerebellum.

Immunoreactive GnRH type I receptors in the mouse and sheep brain.

Gonadotropin Releasing Hormone-I (GnRH) has been implicated in an array of functions outside the neuroendocrine reproductive axis. Previous investigations have reported extensive GnRH binding in numerous sites and this has been supported by in situ hybridization studies reporting GnRH receptor mRNA distribution. The present study on mice and sheep supports and extends these earlier investigations by revealing the distribution of cells immunoreactive for the GnRH receptor.