Chloride cotransporter NKCC1 inhibitor bumetanide protects against white matter injury in a rodent model of periventricular leukomalacia.
Pediatr Res
; 77(4): 554-62, 2015 Apr.
Article
en En
| MEDLINE
| ID: mdl-25585037
ABSTRACT
BACKGROUND:
Periventricular leukomalacia (PVL) is a major form of preterm brain injury. Na(+)-K(+)-Cl(-) 1 cotransporter (NKCC1) expression on neurons and astrocytes is developmentally regulated and mediates Cl(-) reversal potential. We hypothesized that NKCC1 is highly expressed on oligodendrocytes (OLs) and increases vulnerability to hypoxia-ischemia (HI) mediated white matter injury, and that the NKCC1 inhibitor bumetanide would be protective in a rodent PVL model.METHODS:
Immunohistochemistry in Long-Evans rats and PLP-EGFP transgenic mice was used to establish cell-specific expression of NKCC1 in the immature rodent brain. HI was induced on postnatal day 6 (P6) in rats and the protective efficacy of bumetanide (0.3 mg/kg/i.p. q12h × 60 h) established.RESULTS:
NKCC1 was expressed on OLs and subplate neurons through the first 2 postnatal weeks, peaking in white matter and the subplate between P3-7. Following HI, NKCC1 is expressed on OLs and neurons. Bumetanide treatment significantly attenuates myelin basic protein loss and neuronal degeneration 7 d post-HI.CONCLUSION:
Presence and relative overexpression of NKCC1 in rodent cerebral cortex coincides with a period of developmental vulnerability to HI white matter injury in the immature prenatal brain. The protective efficacy of bumetanide in this model of preterm brain injury suggests that Cl(-) transport is a factor in PVL and that its inhibition may have clinical application in premature human infants.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Leucomalacia Periventricular
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Bumetanida
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Corteza Cerebral
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Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico
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Miembro 2 de la Familia de Transportadores de Soluto 12
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Sustancia Blanca
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2015
Tipo del documento:
Article