Idazoxan does not prevent but worsens focal hypoxic-ischemic brain damage in neonatal Wistar rats
✍ Scribed by Daniel Antier; Florence Franconi; Frédéric Sannajust
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 238 KB
- Volume
- 58
- Category
- Article
- ISSN
- 0360-4012
No coin nor oath required. For personal study only.
✦ Synopsis
We examined the neuroprotective efficacy of a posttreatment with idazoxan (Idaz): an ␣2-adrenoceptor antagonist with activity at the I1-and I2-subtypes of the imidazoline receptor (I-receptor), in an experimental model of perinatal hypoxic-ischemic (HI) brain damage. Seventy-two, 7-day-old Wistar rats were subjected to permanent unilateral ligation of the common carotid artery and transient (2 hr) hypoxia (8% O 2 ). The surviving animals were sub-divided into 3 groups: one ''control'' group received intraperitoneal (i.p.) injection of saline (⌺; n ؍ 21) and two ''treated'' groups received, 10 min post-HI, i.p. treatments with Idaz (I3: 3 mg/kg; n ؍ 19) or (I8: 8 mg/kg; n ؍ 20). Idaz effects were assessed by TTC-staining 72 hr post-HI for ⌺ (n ؍ 13), I3 (n ؍ 11), and I8 (n ؍ 12) groups and by MRI-examination 5 weeks post-HI for ⌺ (n ؍ 8), I3 (n ؍ 8), and I8 (n ؍ 6) groups. Total ratio of brain infarct areas were significantly (P F 0.01) different between ⌺ and Idaz-treated rats: 20.9 ؎ 4.0%, 35.6 ؎ 5.9 % and 36.8 ؎ 5.8% for ⌺, I3 and I8, respectively, when determined with TTC-staining and; 23.3 ؎ 3.7%, 39.8 ؎ 4.2%, and 43.2 ؎ 10.1%, for ⌺, I3, and I8, respectively, when assessed by MRI. Our results suggest that Idaz, given as a post-HI treatment, does not exert neuroprotective effects but enhances the brain injury induced by focal neonatal cerebral HI. The deleterious mechanism may result from an overactivity of sympathetic tone and/or the immaturity of central I-receptors in newborn rats.