title: Exacerbation of brain pathology after partial restraint in hypertensive rats following SiO₂ nanoparticles exposure at high ambient temperature.
abstract: This investigation examines the possibility that exposure to silica dust of hypertensive individuals may exacerbate brain pathology and sensory motor dysfunction at high environmental temperature. Hypertension was produced in rats (200-250 g) by two-kidney one clip (2K1C) method, and in these animals, SiO2 nanoparticles (NPs; 50 to 60 nm) were administered at 50 mg/kg, i.p. daily for 1 week. On the 8th day, these rats were subjected to partial restraint in a Perspex box for 4 h either at room temperature (21 °C) or at 33 °C in a biological oxygen demand incubator (wind velocity, 2.6 cm/s; relative humidity, 65 to 67 %). In these animals, behavioral functions, blood-brain barrier (BBB) permeability to Evans blue albumin (EBA) and radioiodine (([131]-)Iodine), brain water content and neuronal injuries were determined. Hypertensive rats subjected to 4 h restraint at room temperature did not exhibit BBB dysfunction, brain edema, neural injury, or alterations in rotarod or inclined plane angle performances. However, when these hypertensive rats were subjected to restraint at 33 °C, breakdown of the cortical BBB (EBA, +38 %; radioiodine, +56 %), brain water (+0.88 %), neuronal damages (+18 %), and behavioral impairment were exacerbated. Interestingly, SiO2 exposure to these rats further exacerbated BBB breakdown (EBA, 280 %; radioiodine, 350 %), brain edema (4 %), and neural injury (30 %) after identical restraint depending on the ambient temperature. SiO2 treatment also induced brain pathology and alteration in behavioral functions in normotensive rats after restraint at high temperature. These observations clearly show that hypertension significantly enhances restraint-induced brain pathology, and behavioral anomalies particularly at high ambient temperature and SiO2 intoxication further exacerbated these brain pathologies and cognitive dysfunctions.
authors.affiliation: Laboratory of Cerebrovascular Research, Departmen of Surgical Sciences, Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, Frödingsgatan 12, 75421, Uppsala, Sweden, Sharma@surgsci.uu.se.
authors.forename: Hari S
authors.initials: HS
authors.lastname: Sharma
authors.forename: Dafin F
authors.initials: DF
authors.lastname: Muresanu
authors.forename: Ranjana
authors.initials: R
authors.lastname: Patnaik
authors.forename: Aruna
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D001929:Brain Edema / Q000097:blood / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004781:Environmental Exposure; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D053758:Nanoparticles / Q000009:adverse effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012149:Restraint, Physical; D045442:Rotarod Performance Test; D012822:Silicon Dioxide / Q000009:adverse effects*; D013315:Stress, Psychological / Q000097:blood / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D013696:Temperature
chemical_list: D001786:Blood Glucose; D012822:Silicon Dioxide