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1.
J Neurosci Res ; 99(11): 2964-2975, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34487578

RESUMEN

The cellular responses to hypoxia or hypoxia-ischemia (HI) are governed largely by the hypoxia-inducible factor (HIF) family of transcription factors. Our previous studies show that HIF-1α induction is an important factor that mediates protective effects in the brain after neonatal HI. In the present study, we investigated the contribution of another closely related HIF α isoform, HIF-2α, specifically the neuronal HIF-2α, to brain HI injury. Homozygous transgenic mice with a floxed exon 2 of HIF-2α were bred with CaMKIIα-Cre mice to generate a mouse line with selective deletion of HIF-2α in forebrain neurons. These mice, along with their wildtype littermates, were subjected to HI at postnatal day 9. Brain injury at different ages was evaluated by the levels of cleaved caspase-3 and spectrin breakdown products at 24 hr; and histologically at 6 days or 3 months after HI. Multiple behavioral tests were performed at 3 months, prior to sacrifice. Loss of neuronal HIF-2α exacerbated brain injury during the acute (24 hr) and subacute phases (6 days), with a trend toward more severe volume loss in the adult brain. The long-term brain function for coordinated movement and recognition memory, however, were not impacted in the neuronal HIF-2α deficient mice. Our data suggest that, similar to HIF-1α, neuronal HIF-2α promotes cell survival in the immature mouse brain. The two HIF alpha isoforms may act through partially overlapping or distinct transcriptional targets to mediate their intrinsic protective responses against neonatal HI brain injury.


Asunto(s)
Lesiones Encefálicas , Neuronas , Animales , Animales Recién Nacidos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Lesiones Encefálicas/metabolismo , Hipoxia/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Ratones Transgénicos , Neuronas/metabolismo
2.
Dev Neurosci ; 40(5-6): 437-450, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30995639

RESUMEN

Brain damage after hypoxia-ischemia (HI) occurs in an age-dependent manner. Neuroprotective strategies assumed to be effective in adults might have deleterious effects in the immature brain. In order to create effective therapies, the complex pathophysiology of HI in the developing brain requires exploring new mechanisms. Critical determinants of neuronal survival after HI are the extent of vascular dysfunction, inflammation, and oxidative stress, followed later by tissue repair. The key enzyme of these processes in the human body is arginase (ARG) that acts via the bioavailability of nitric oxide, and the synthesis of polyamines and proline. ARG is expressed throughout the brain in different cells. However, little is known about the effect of ARG in pathophysiological states of the brain, especially hypoxia-ischemia. Here, we summarize the role of ARG during neurodevelopment as well as in various brain pathologies.

3.
Am J Mens Health ; 5(4): 306-17, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20798145

RESUMEN

Qualitative research has rarely explored gender-based concerns of men with disabilities. Accordingly, this research investigates body image and self-concept for men with an acquired spinal cord injury (SCI). Modified grounded theory analysis was conducted for secondary, qualitative interview data of 64 male participants from a study of community dwellers living with SCI. Three major themes related to body image and self-concept emerged: consequences for self due to bodily changes, interactions with the public, and decisions and actions people take. Findings indicate that rehabilitation services should include ongoing research to explore the unique needs of male clients. Findings also have implications for rehabilitation therapists and their roles in addressing gender-based concerns of the male client.


Asunto(s)
Adaptación Psicológica , Imagen Corporal , Autoimagen , Traumatismos de la Médula Espinal/psicología , Estrés Psicológico , Estudios Transversales , Identidad de Género , Humanos , Masculino , Investigación Cualitativa , Factores Sexuales , Estados Unidos/epidemiología
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