Long-Term Comorbid Neuropsychiatric Sequelae of Hypoxia at Birth.

Perinatal hypoxia due to obstetric complications has been known to cause neurodevelopmental impairments in infants and children. The severity of the impairments and recovery depends on the degree of hypoxia. There have been some studies which focuses on understanding the effects of perinatal hypoxia on cognitive and behavioral functioning like attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), learning disorders, or aggression. Although the studies have investigated the effects in children, there are very few studies done to explore perinatal hypoxia, causing any neuropsychiatric outcomes in adults.  This is a case of a 38-year-old man who presented to psychiatry as a referral for depression by neurology. He saw neurology for intractable migraine resistant to all treatment for the last year. The brain imaging was read as normal with minor small vascular changes. During our assessment, he reported depression and passive suicidal ideation, which began since he was diagnosed with migraines. His developmental history was significant for perinatal asphyxia and learning difficulties. Growing up, he reported severe irritability, impulsivity, and risk-taking behaviors but became stable when he was in his late twenties. His past psychiatric management was unclear. He was seeing an outpatient therapist when he visited our clinic. We diagnosed him with an unspecified mood disorder, tried prozac, and then gabapentin with some effect. Before we could explore further medication trials with topamax, his care had to be transferred to other psychiatrists, and we could not obtain further details of his outcome.  Based on our case, we concluded there is a need for further research focused on the effects of perinatal hypoxia on certain brain areas as a cause of neuropsychiatric symptoms in adults.

Astrocyte progenitor transplantation promotes regeneration of bulbospinal respiratory axons, recovery of diaphragm function, and a reduced macrophage response following cervical spinal cord injury.

Stem/progenitor cell transplantation delivery of astrocytes is a potentially powerful strategy for spinal cord injury (SCI). Axon extension into SCI lesions that occur spontaneously or in response to experimental manipulations is often observed along endogenous astrocyte "bridges," suggesting that augmenting this response via astrocyte lineage transplantation can enhance axon regrowth. Given the importance of respiratory dysfunction post-SCI, we transplanted glial-restricted precursors (GRPs)-a class of lineage-restricted astrocyte progenitors-into the C2 hemisection model and evaluated effects on diaphragm function and the growth response of descending rostral ventral respiratory group (rVRG) axons that innervate phrenic motor neurons (PhMNs). GRPs survived long term and efficiently differentiated into astrocytes in injured spinal cord. GRPs promoted significant recovery of diaphragm electromyography amplitudes and stimulated robust regeneration of injured rVRG axons. Although rVRG fibers extended across the lesion, no regrowing axons re-entered caudal spinal cord to reinnervate PhMNs, suggesting that this regeneration response-although impressive-was not responsible for recovery. Within ipsilateral C3-5 ventral horn (PhMN location), GRPs induced substantial sprouting of spared fibers originating in contralateral rVRG and 5-HT axons that are important for regulating PhMN excitability; this sprouting was likely involved in functional effects of GRPs. Finally, GRPs reduced the macrophage response (which plays a key role in inducing axon retraction and limiting regrowth) both within the hemisection and at intact caudal spinal cord surrounding PhMNs. These findings demonstrate that astrocyte progenitor transplantation promotes significant plasticity of rVRG-PhMN circuitry and restoration of diaphragm function and suggest that these effects may be in part through immunomodulation.

Sieving characteristics of cytokine- and peroxide-induced epithelial barrier leak: Inhibition by berberine.

AIM: To study whether the inflammatory bowel disease (IBD) colon which exhibits varying severity and cytokine levels across its mucosa create varying types of transepithelial leak. METHODS: We examined the effects of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1-ß (IL1ß) and hydrogen peroxide (H2O2) - singly and in combinations - on barrier function of CACO-2 cell layers. Our focus was on the type (not simply the magnitude) of transepithelial leak generated by these agents as measured by transepithelial electrical resistance (TER) and transepithelial flux of (14)C-D-mannitol, (3)H-Lactulose and (14)C-Polyethylene glycol as radiolabeled probe molecules. The isoquinoline alkaloid, berberine, was then examined for its ability to reduce specific types of transepithelial leak. RESULTS: Exposure to TNF-α alone (200 ng/mL; 48 h) induced a 50% decrease in TER, i.e., increased leak of Na(+) and Cl(-) - with only a marginal but statistically significant increase in transepithelial leak of (14)C-mannitol (Jm). Exposure to TNF-α + IFN-γ (200 ng/mL; 48 h) + IL1ß (50 ng/mL; 48 h) did not increase the TER change (from TNF-α alone), but there was now a 100% increase in Jm. There however was no increase in transepithelial leak of two larger probe molecules, (3)H-lactulose and (14)C-polyethylene glycol (PEG). However, exposure to TNF-α + IFN-γ + IL1ß followed by a 5 h exposure to 2 mmol/L H2O2 resulted in a 500% increase in (14)C-PEG leak as well as leak to the luminal mitogen, epidermal growth factor. CONCLUSION: This model of graded transepithelial leak is useful in evaluating therapeutic agents reducing IBD morbidity by reducing barrier leak to various luminal substances.