title: Impact of experimental acute hyponatremia on severe traumatic brain injury in rats: influences on injuries, permeability of blood-brain barrier, ultrastructural features, and aquaporin-4 expression.
abstract: The effects of acute hyponatremia on severe traumatic brain injury (TBI) in 35 adult male Sprague-Dawley rats were studied in a replicated focal and diffuse injury rat model. Such effects were assessed by the cerebral contusion volume and axonal injury (AI) densities, determined by quantitative immunoreactivity of beta-amyloid precursor protein, by blood-brain barrier (BBB) permeability based on endogenous IgG immunostaining, and by ultrastructural features. Significant increase of contusion volume (P < 0.05) and of AI in the segment of corpus callosum beneath the contusion (P < 0.05) and ipsilateral thalamus (P < 0.05) were observed at 4 h postinjury during the hyponatremic phase. No change in BBB permeability was observed in the hyponatremia + TBI (HT) groups. Significant swelling of perivascular astrocytic foot processes in the HT groups was seen at 4 h (P < 0.01) and 1 day postinjury (P < 0.01) by quantitative image analysis of ultrastructures. However, attenuated swelling of perivascular astrocytic foot processes in severely edematous medulla oblongata with simultaneous swelling of perikaryal astrocytic processes was observed in the HT 1-day group. The ultrastructural features were also correlated with the down-regulation of aquaporin-4 (AQP4) mRNA expression (P < 0.05). Results suggest that acute hyponatremia acts as one of the secondary insults following severe TBI. Such exacerbation may not be attributable to further disruption of BBB permeability, but rather to the ischemia resulting from the swelling of perivascular astrocytic foot processes impeding microcirculation. Down-regulated AQP4 mRNA expression may be one of the molecular mechanisms maintaining water homeostasis in diffusely injured brain exposed to acute hyponatremia.
authors.affiliation: Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong.
authors.forename: Changshu
authors.initials: C
authors.lastname: Ke
authors.forename: Wai Sang
authors.initials: WS
authors.lastname: Poon
authors.forename: Ho Keung
authors.initials: HK
authors.lastname: Ng
authors.forename: Fernand M M
authors.initials: FM
authors.lastname: Lai
authors.forename: Nelson L S
authors.initials: NL
authors.lastname: Tang
authors.forename: Jesse C S
authors.initials: JC
authors.lastname: Pang
mesh_terms: D000208:Acute Disease; D000818:Animals; D051401:Aquaporin 4; D020346:Aquaporins / Q000096:biosynthesis*; D001812:Blood-Brain Barrier / Q000502:physiology*; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D002199:Capillary Permeability / Q000502:physiology; D007010:Hyponatremia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D012333:RNA, Messenger