{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T23:24:13Z","timestamp":1778282653665,"version":"3.51.4"},"reference-count":33,"publisher":"S. Karger AG","issue":"3-4","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev Neurosci"],"published-print":{"date-parts":[[2011]]},"abstract":"<jats:p>Cerebral palsy and death are serious consequences of perinatal hypoxia-ischemia (HI). Important concepts can now be tested using an animal model of cerebral palsy. We have previously shown that reactive oxygen and nitrogen species are produced in antenatal HI. A novel class of neuronal nitric oxide synthase (nNOS) inhibitors have been designed, and they ameliorate postnatal motor deficits when administered prior to the hypoxic-ischemic insult. This study asks how the new class of inhibitors, using JI-8 (K&lt;sub&gt;i&lt;\/sub&gt; for nNOS: 0.014 \u00b5&lt;i&gt;M&lt;\/i&gt;) as a representative, compare with the frequently used nNOS inhibitor 7-nitroindazole (7-NI; K&lt;sub&gt;i&lt;\/sub&gt;: 0.09 \u00b1 0.024 \u00b5&lt;i&gt;M&lt;\/i&gt;). A theoretical dose equivalent to 75 K&lt;sub&gt;i&lt;\/sub&gt; of JI-8 or equimolar 7-NI was administered to pregnant rabbit dams 30 min prior to and immediately after 40 min of uterine ischemia at 22 days gestation (70% term). JI-8 treatment resulted in a significant decrease in NOS activity (39%) in fetal brain homogenates acutely after HI, without affecting maternal blood pressure and heart rate. JI-8 treatment resulted in 33 normal kits, 2 moderately and 13 severely affected kits and 5 stillbirths, compared with 8 normal, 3 moderately affected and 5 severely affected kits and 10 stillbirths in the 7-NI group. In terms of neurobehavioral outcome, 7-NI was not different from saline treatment, while JI-8 was superior to saline and 7-NI in its protective effect (p &lt; 0.05). In the surviving kits, JI-8 significantly improved the locomotion score over both saline and 7-NI scores. JI-8 was also significantly superior to saline in preserving smell, muscle tone and righting reflex function, but 7-NI did not show significant improvement. Furthermore, a 100-fold increase in the dose (15.75 \u00b5mol\/kg) of 7-NI significantly decreased systolic blood pressure in the dam, while JI-8 did not. The new class of inhibitors such as JI-8 shows promise in the prevention of cerebral palsy and is superior to the previously more commonly used nNOS inhibitor.<\/jats:p>","DOI":"10.1159\/000327244","type":"journal-article","created":{"date-parts":[[2011,6,10]],"date-time":"2011-06-10T12:40:47Z","timestamp":1307709647000},"page":"312-319","source":"Crossref","is-referenced-by-count":38,"title":["Neuronal Nitric Oxide Synthase Inhibition Prevents Cerebral Palsy following Hypoxia-Ischemia in Fetal Rabbits: Comparison between JI-8 and 7-Nitroindazole"],"prefix":"10.1159","volume":"33","author":[{"given":"Lei","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Derrick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haitao","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard 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