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.
This model of graded transepithelial leak is useful in evaluating therapeutic agents reducing IBD morbidity by reducing barrier leak to various luminal substances.
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.
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