Pioglitazone restores mitochondrial function but does not spare cortical tissue following mild brain contusion.

Pioglitazone interacts through the mitochondrial protein mitoNEET to improve brain bioenergetics following traumatic brain injury. To provide broader evidence regarding the therapeutic effects of pioglitazone after traumatic brain injury, the current study is focused on immediate and delayed therapy in a model of mild brain contusion. To assess pioglitazone therapy on mitochondrial bioenergetics in cortex and hippocampus, we use a technique to isolate subpopulations of total, glia-enriched and synaptic mitochondria.

Clinically relevant mitochondrial-targeted therapy improves chronic outcomes after traumatic brain injury.

Pioglitazone, an FDA-approved compound, has been shown to target the novel mitochondrial protein mitoNEET and produce short-term neuroprotection and functional benefits following traumatic brain injury. To expand on these findings, we now investigate the dose- and time-dependent effects of pioglitazone administration on mitochondrial function after experimental traumatic brain injury. We then hypothesize that optimal pioglitazone dosing will lead to ongoing neuroprotection and cognitive benefits that are dependent on pioglitazone-mitoNEET signalling pathways.

Temporal changes in inflammatory mitochondria-enriched microRNAs following traumatic brain injury and effects of miR-146a nanoparticle delivery.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate post-transcriptional gene expression and contribute to all aspects of cellular function. We previously reported that the activities of several mitochondria-enriched miRNAs regulating inflammation (i.e.

Formoterol, a β-adrenoreceptor agonist, induces mitochondrial biogenesis and promotes cognitive recovery after traumatic brain injury.

Traumatic brain injury (TBI) leads to acute necrosis at the site of injury followed by a sequence of secondary events lasting from hours to weeks and often years. Targeting mitochondrial impairment following TBI has shown improvements in brain mitochondrial bioenergetics and neuronal function. Recently formoterol, a highly selective β-adrenoreceptor agonist, was found to induce mitochondrial biogenesis (MB) via Gβγ-Akt-eNOS-sGC pathway.

Acute Mitochondrial Impairment Underlies Prolonged Cellular Dysfunction after Repeated Mild Traumatic Brain Injuries.

Mild traumatic brain injuries (mTBI), accounting for more than 80% of TBIs, can cause cognitive and behavioral impairments, the severity and duration of which increase after additional mTBIs. While mTBI does not cause widespread neuronal death, the mechanisms underlying increased cellular susceptibility to subsequent head impacts remain unknown. To investigate the hypothesis that altered mitochondrial bioenergetics underlie cellular vulnerability to repeated insults, we employed a mouse model of mild closed head injury (CHI) to examine mitochondrial function and oxidative stress, because these mechanisms are often intertwined.

Effects of a docosahexaenoic acid-rich microalgae nutritional product on insulin sensitivity after prolonged dexamethasone treatment in healthy mature horses.

Objective: To determine effects of a microalgae nutritional product on insulin sensitivity in horses.

Animals: 8 healthy mature horses. PROCEDURES :Horses (n = 4/group) received a basal diet without (control diet) or with docosahexaenoic acid-rich microalgae meal (150 g/d) for 49 days (day 0 = first day of diet).

Stem cell factor rescues tyrosinase expression and pigmentation in discreet anatomic locations in albino mice.

The K14-SCF transgenic murine model of variant pigmentation is based on epidermal expression of stem cell factor (SCF) on the C57BL/6J background. In this system, constitutive expression of SCF by epidermal keratinocytes results in retention of melanocytes in the interfollicular basal layer and pigmentation of the epidermis itself. Here, we extend this animal model by developing a compound mutant transgenic amelanotic animal defective at both the melanocortin 1 receptor (Mc1r) and tyrosinase (Tyr) loci.

In vitro skin diffusion study of pure forskolin versus a forskolin-containing Plectranthus barbatus root extract.

An in vitro skin diffusion study of pure forskolin (1) versus a 1-containing Plectranthus barbatus root extract (P. barbatus extract) in hairless guinea pig skin and human skin in a flow-through diffusion cell system was conducted and is being reported for the first time. Both topical agents were formulated in a solution of 70% ethanol and 30% propylene glycol (v/v).

Prolonged treatment of fair-skinned mice with topical forskolin causes persistent tanning and UV protection.

We previously reported that topical application of forskolin to the skin of fair-skinned MC1R-defective mice with epidermal melanocytes resulted in accumulation of eumelanin in the epidermis and was highly protective against UV-mediated cutaneous injury. In this report, we describe the long-term effects of chronic topical forskolin treatment in this animal model. Forskolin-induced eumelanin production persisted through 3 months of daily applications, and forskolin-induced eumelanin remained protective against UV damage as assessed by minimal erythematous dose (MED).

DNA repair pathways and hereditary cancer susceptibility syndromes.

Every living organism is exposed to numerous genomic insults on a daily basis as a consequence of cellular metabolism and exposure to environmental agents capable of interacting with the genome (e.g. chemicals, toxins, pollutants, UV and ionizing radiation) (1).

Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning.

Ultraviolet-light (UV)-induced tanning is defective in numerous 'fair-skinned' individuals, many of whom contain functional disruption of the melanocortin 1 receptor (MC1R). Although this suggested a critical role for the MC1R ligand melanocyte stimulating hormone (MSH) in this response, a genetically controlled system has been lacking in which to determine the precise role of MSH-MC1R. Here we show that ultraviolet light potently induces expression of MSH in keratinocytes, but fails to stimulate pigmentation in the absence of functional MC1R in red/blonde-haired Mc1r(e/e) mice.