Idazoxan does not prevent but worsens focal hypoxic-ischemic brain damage in neonatal Wistar rats

• Published in: Journal of neuroscience research Vol. 58; no. 5; pp. 690 - 696
• Main Authors: Antier, Daniel, Franconi, Florence, Sannajust, Frédéric
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.12.1999
• Subjects: Animals; Animals, Newborn; Brain - pathology; Brain Ischemia - drug therapy; Brain Ischemia - pathology; idazoxan; Idazoxan - adverse effects; Idazoxan - therapeutic use; Magnetic Resonance Imaging; neonatal focal cerebral hypoxia-ischemia; rat; Rats; Rats, Wistar; TTC-staining
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/(SICI)1097-4547(19991201)58:5<690::AID-JNR10>3.0.CO;2-L

We examined the neuroprotective efficacy of a post‐treatment with idazoxan (Idaz): an α2‐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% O2). The surviving animals were sub‐divided into 3 groups: one “control” group received intraperitoneal (i.p.) injection of saline (Σ; 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 Σ (n = 13), I3 (n = 11), and I8 (n = 12) groups and by MRI‐examination 5 weeks post‐HI for Σ (n = 8), I3 (n = 8), and I8 (n = 6) groups. Total ratio of brain infarct areas were significantly (P < 0.01) different between Σ and Idaz‐treated rats: 20.9 ± 4.0%, 35.6 ± 5.9 % and 36.8 ± 5.8% for Σ, I3 and I8, respectively, when determined with TTC‐staining and; 23.3 ± 3.7%, 39.8 ± 4.2%, and 43.2 ± 10.1%, for Σ, 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. J. Neurosci. Res. 58:690–696, 1999. © 1999 Wiley‐Liss, Inc.