Hypoxic-ischemic injury decreases anxiety-like behavior in rats when associated with loss of tyrosine-hydroxylase immunoreactive neurons of the substantia nigra

Abstract

Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI), and severe HI groups (N = 10 in each group at each time) on postnatal day 7 (P7) to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH) in the substantia nigra (SN). The mild and severe HI groups were exposed to hypoxia (8% O2/92% N2) for 90 and 150 min, respectively. The elevated plus-maze (EPM) test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT) and OAT%, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT% in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold) and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05). The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2%) and severe HI groups (16.3, 32.2, and 43.8%, respectively; P < 0.05). The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group) with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI.

Palmitoylethanolamide prevents neuroinflammation, reduces astrogliosis and preserves recognition and spatial memory following induction of neonatal anoxia-ischemia

“…It is important to note that, unlike other authors (Ming-Yan et al 2012;Sedláčková et al 2014), we did not find changes in anxiety-related behaviors. However, this is consistent with previous results from our group in another model of global hypoxia-ischemia (Galeano et al 2011).…”

Maternal Cigarette Smoke Exposure Worsens Neurological Outcomes in Adolescent Offspring with Hypoxic-Ischemic Injury

“…Our result is somewhat consistent with this study where the decline in short-term memory function was not remarkable at P40–44, suggesting that neural plasticity is more resilient to neonatal HI injury. HI injury regardless of its severity, was found to reduce anxiety-like behavior in Sprague-Dawley rats due to decreased activity of tyrosine hydroxylase in the substantia nigra ( Hei et al, 2012 ). However, in the current study, HI injury had no effect on the anxiety levels in HI offspring.…”

Long-Term Recovery After Endothelial Colony-Forming Cells or Human Umbilical Cord Blood Cells Administration in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

“…The elevated plus maze (EPM) test was performed on P21 ( n = 10/group) to evaluate animal anxiety as previously described . The EPM apparatus consists of two open arms (50 × 10 × 1 cm) and two closed arms (50 × 10 × 40 cm) crossing on a common central platform (10 × 10 cm) forming a plus shape, elevated to 50 cm above the floor.…”