Proteasome localization and activity in pig brain and small molecule screening for activators.

Introduction: Loss of proteasome function, proteinopathy, and proteotoxicity may cause neurodegeneration across the human lifespan in several forms of brain injury and disease. Drugs that activate brain proteasomes could thus have a broad therapeutic impact in neurology.

Methods: Using pigs, a clinically relevant large animal with a functionally compartmental gyrencephalic cerebral cortex, we evaluated the localization and biochemical activity of brain proteasomes and tested the ability of small molecules to activate brain proteasomes.

Importance of Control Groups for Evaluating Long-Term Behavioral and Cognitive Outcomes of Controlled Cortical Impact in Immature Rats.

Therapies are limited for pediatric traumatic brain injury (TBI), especially for the very young who can experience long-term consequences to learning, memory, and social behavior. Animal models of pediatric TBI have yielded mechanistic insights, but demonstration of clinically relevant long-term behavioral and/or cognitive deficits has been challenging. We characterized short- and long-term outcomes in a controlled cortical impact (CCI) model of pediatric TBI using a panel of tests between 2 weeks and ∼4 months after injury.

Oleuropein Activates Neonatal Neocortical Proteasomes, but Proteasome Gene Targeting by AAV9 Is Variable in a Clinically Relevant Piglet Model of Brain Hypoxia-Ischemia and Hypothermia.

Cerebral hypoxia-ischemia (HI) compromises the proteasome in a clinically relevant neonatal piglet model. Protecting and activating proteasomes could be an adjunct therapy to hypothermia. We investigated whether chymotrypsin-like proteasome activity differs regionally and developmentally in the neonatal brain.

Surgical Decompression for Cervical Spondylotic Myelopathy in Patients with Associated Hypertension: A Single-Center Retrospective Cohort and Systematic Review of the Literature.

Objective: To explore the relationship between spinal cord compression and hypertension through analysis of blood pressure (BP) variations in a cervical spondylotic myelopathy (CSM) cohort after surgical decompression, along with a review of the literature.

Methods: A single-institution retrospective review of patients with CSM who underwent cervical decompression between 2016 and 2017 was conducted. Baseline clinical and imaging characteristics, preoperative and postoperative BP readings, heart rate, functional status, and pain scores were collected.

Novel therapeutics for brain tumors: current practice and future prospects.

: Malignant gliomas are the most common and aggressive primary brain tumor with current available therapies increasing median survival to a modest 20 months. Multiple preclinical research efforts aim to further this improvement through advances in therapeutic options for these patients.: The unique obstacles that must be managed in developing and delivering safe and efficacious therapeutics into the central nervous system are reviewed.

Time to reconsider extended erythropoietin treatment for infantile traumatic brain injury?

Pediatric traumatic brain injury (TBI) remains a leading cause of childhood morbidity and mortality worldwide. Most efforts to reduce the chronic impact of pediatric TBI involve prevention and minimization of secondary injury. Currently, no treatments are used in routine clinical care during the acute and subacute phases to actively repair injury to the developing brain.

Sex differences in pediatric traumatic brain injury.

The response of the developing brain to traumatic injury is different from the response of the mature, adult brain. There are critical developmental trajectories in the young brain, whereby injury can lead to long term functional abnormalities. Emerging preclinical and clinical literature supports the presence of significant sex differences in both the response to and the recovery from pediatric traumatic brain injury (TBI).

Extended Combined Neonatal Treatment With Erythropoietin Plus Melatonin Prevents Posthemorrhagic Hydrocephalus of Prematurity in Rats.

Posthemorrhagic hydrocephalus of prematurity (PHHP) remains a global challenge. Early preterm infants (<32 weeks gestation), particularly those exposed to chorioamnionitis (CAM), are prone to intraventricular hemorrhage (IVH) and PHHP. We established an age-appropriate, preclinical model of PHHP with progressive macrocephaly and ventriculomegaly to test whether non-surgical neonatal treatment could modulate PHHP.

The contribution of TRPV1 channel to 20-HETE-Aggravated ischemic neuronal injury.

20-Hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P450 (CYP) 4A/4F-derived metabolite of arachidonic acid, directly contributes to ischemic neuronal injury. However, little is known about mediators of 20-HETE neurotoxicity after ischemia. Here, we focus on the role of transient receptor potential cation channel subfamily V member 1 (TRPV1) in 20-HETE-induced neurotoxicity.