Rodent Estrous Cycle Monitoring Utilizing Vaginal Lavage: No Such Thing As a Normal Cycle.

The current methodology establishes a reproducible, standardized, and cost-effective approach to monitoring the estrous cycle of female Sprague Dawley (SD) adolescent rats. This study demonstrates the complexity of hormonal cycles and the broad spectrum of understanding required to construct a reliable and valid monitoring technique. Through an in-depth examination of principal experimental design and procedural elements, this description of the cycle and its fundamental principles provides a framework for further understanding and deconstructs misconceptions for future replication.

Sex Differences in Neurophysiological Changes Following Voluntary Exercise in Adolescent Rats.

Adolescence is a period of time characterized by the onset of puberty and is marked by cognitive and social developments and gross physical changes that can play a role in athletic performance. Sex differences are present with differences in body size, height, physiology and behavior which contribute to differences in athletic performance as well. Pre-clinical studies representing this active group are lacking.

Pathophysiology of Pediatric Traumatic Brain Injury.

The national incidence of traumatic brain injury (TBI) exceeds that of any other disease in the pediatric population. In the United States the Centers for Disease Control and Prevention (CDC) reports 697,347 annual TBIs in children ages 0-19 that result in emergency room visits, hospitalization or deaths. There is a bimodal distribution within the pediatric TBI population, with peaks in both toddlers and adolescents.

Recovery From Repeat Mild Traumatic Brain Injury in Adolescent Rats Is Dependent on Pre-injury Activity State.

Adolescents and young adults have the highest incidence of mild traumatic brain injury (mTBI); sport-related activities are a major contributor. Roughly a third of these patients diagnosed with mTBI are estimated to have received a subsequent repeat mTBI (rTBI). Previously, animal studies have only modeled mTBI in sedentary animals.

Alternative substrate metabolism depends on cerebral metabolic state following traumatic brain injury.

Decreases in energy metabolism following traumatic brain injury (TBI) are attributed to impairment of glycolytic flux and oxidative phosphorylation. Glucose utilization post-TBI is decreased while administration of alternative substrates has been shown to be neuroprotective. Changes in energy metabolism following TBI happens in two phases; a period of hyper-metabolism followed by prolonged hypo-metabolism.

Transcriptional activation of antioxidant gene expression by Nrf2 protects against mitochondrial dysfunction and neuronal death associated with acute and chronic neurodegeneration.

Mitochondria are both a primary source of reactive oxygen species (ROS) and a sensitive target of oxidative stress; damage to mitochondria can result in bioenergetic dysfunction and both necrotic and apoptotic cell death. These relationships between mitochondria and cell death are particularly strong in both acute and chronic neurodegenerative disorders. ROS levels are affected by both the production of superoxide and its toxic metabolites and by antioxidant defense mechanisms.

Concussion: pathophysiology and clinical translation.

The majority of the 3.8 million estimated annual traumatic brain injuries (TBI) in the United States are mild TBIs, or concussions, and they occur primarily in adolescents and young adults. A concussion is a brain injury associated with rapid brain movement and characteristic clinical symptoms, with no associated objective biomarkers or overt pathologic brain changes, thereby making it difficult to diagnose by neuroimaging or other objective diagnostic tests.

Repeat Mild Traumatic Brain Injury in Adolescent Rats Increases Subsequent β-Amyloid Pathogenesis.

Single moderate-to-severe traumatic brain injuries (TBIs) may increase subsequent risk for neurodegenerative disease by facilitating β-amyloid (Aβ) deposition. However, the chronic effects on Aβ pathogenesis of repetitive mild TBIs (rTBI), which are common in adolescents and young adults, remain uncertain. We examined the effects of rTBI sustained during adolescence on subsequent deposition of Aβ pathology in a transgenic APP/PS1 rat model.

Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity.

Cerebral metabolism of ketones after traumatic brain injury (TBI) improves neuropathology and behavior in an age-dependent manner. Neuroprotection is attributed to improved cellular energetics, although other properties contribute to the beneficial effects. Oxidative stress is responsible for mitochondrial dysfunction after TBI.

Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed.

The pathophysiology of traumatic brain injury at a glance.

Traumatic brain injury (TBI) is defined as an impact, penetration or rapid movement of the brain within the skull that results in altered mental state. TBI occurs more than any other disease, including breast cancer, AIDS, Parkinson's disease and multiple sclerosis, and affects all age groups and both genders. In the US and Europe, the magnitude of this epidemic has drawn national attention owing to the publicity received by injured athletes and military personnel.

The effects of repeat traumatic brain injury on the pituitary in adolescent rats.

Adolescents are one of the highest groups at risk for sustaining both traumatic brain injury (TBI) and repeat TBI (RTBI). Consequences of endocrine dysfunction following TBI have been routinely explored in adults, but studies in adolescents are limited, and show an incidence rate of endocrine dysfunction in 16-61% in patients, 1-5 years after injury. Similar to in adults, the most commonly affected axis is growth hormone (GH) and insulin-like growth hormone 1 (IGF-1).

Traumatic brain injury and diet.

Increasing attention is being paid to nutritional and metabolic management of traumatic brain injury patients. The gross metabolic changes that occur after injury have been found to be influenced by both macronutrients, that is, dietary ratios of fat, carbohydrates, and protein, and micronutrients, for example, vitamins and minerals. Alterations in diet and nutritional strategies have been shown to decrease both morbidity and mortality after injury.

Sulforaphane inhibits mitochondrial permeability transition and oxidative stress.

Exposure of mitochondria to oxidative stress and elevated Ca(2+) promotes opening of the mitochondrial permeability transition pore (PTP), resulting in membrane depolarization, uncoupling of oxidative phosphorylation, and potentially cell death. This study tested the hypothesis that treatment of rats with sulforaphane (SFP), an activator of the Nrf2 pathway of antioxidant gene expression, increases the resistance of liver mitochondria to redox-regulated PTP opening and elevates mitochondrial levels of antioxidants. Rats were injected with SFP or drug vehicle and liver mitochondria were isolated 40h later.

Brain mitochondria from rats treated with sulforaphane are resistant to redox-regulated permeability transition.

Oxidative stress promotes Ca2+-dependent opening of the mitochondrial inner membrane permeability transition pore (PTP), causing bioenergetic failure and subsequent cell death in many paradigms, including those related to acute brain injury. One approach to pre-conditioning against oxidative stress is pharmacologic activation of the Nrf2/ARE pathway of antioxidant gene expression by agents such as sulforaphane (SFP). This study tested the hypothesis that administration of SFP to normal rats increases resistance of isolated brain mitochondria to redox-sensitive PTP opening.

Neuroprotection through stimulation of mitochondrial antioxidant protein expression.

Oxidative stress and loss of cellular Ca2+ homeostasis are closely linked and are common denominators in the pathophysiology of many neurodegenerative diseases and acute disorders of the nervous system. Mitochondria are major targets of oxidative stress and abnormal intracellular Ca2+, as both can cause bioenergetic failure through synergistic activation of the mitochondrial inner membrane permeability transition pore. Opening of this molecularly ill-defined pore causes both collapse of the membrane potential, which drives oxidative phosphorylation, and release of small metabolites, including pyridine nucleotides and glutathione, which are necessary for energy metabolism and defense against oxidative stress.