Research Report
Effect of prenatal exposure to an anti-inflammatory drug on
neuron number in cornu ammonis and dentate gyrus of the rat
hippocampus: A stereological study
Alpaslan Gokcimen
a
, Murat Çetin Rağbetli
b
, Orhan Baş
c
, Ayten Turkkanı Tunc
d
,
Huseyin Aslan
d
, A. Canan Yazici
e
, Suleyman Kaplan
f,
⁎
a
Department of Histology and Embryology, Süleyman Demirel University School of Medicine, Isparta, Turkey
b
Department of Histology and Embryology, Yüzüncü Yıl University School of Medicine, Van, Turkey
c
Department of Anatomy, Kocatepe University School of Medicine, Afyon, Turkey
d
Department of Histology and Embryology, Gaziosmanpasa University School of Medicine, Tasliciflik Kampusu, Tokat, Turkey
e
Department of Biostatistics, Baskent University School of Medicine, Ankara, Turkey
f
Department of Histology and Embryology, Ondokuz Mayis University School of Medicine, TR-55139 Samsun, Turkey
ARTICLE INFO ABSTRACT
Article history:
Accepted 17 October 2006
Available online 21 November 2006
Prenatal exposed to an anti-inflammatory drug is a major problem for the developing
central nervous system. It is not well known the effect of prenatal exposed to a non-steroidal
anti-inflammatory drug on the hippocampus. Total neuron number in one side of the cornu
ammonis (CA) and gyrus dentatus (GD) of the hippocampal formation in control and drug-
treated (diclofenac sodium, DS) groups of male rats was estimated using the optical
fractionator technique. Each main group has also two subgroups that are 4 weeks old (4W-
old) and 20 weeks old (20W-old). In CA, no significant difference between 4W-old DS-treated
and their control was found, but a significant difference was observed between 20W-old DS-
treated and their controls. A decreasing of neuron number was 12% for 20W-old DS-treated
group. In GD, a decreasing of the granule cell number in 4W-old of DS-treated group was
seen but an increasing of granule cell number was found in the 20W-old drug-treated rats in
comparison to its control group, 7% and 9%, respectively. Although an increasing of neuron
number in CA at the control group was seen with age, from 4th week to 20th week (10%), age-
dependent substantial granule cell decline (17%) was observed in GD. No age effect on the
total cell numbers of CA and GD of the drug-treated groups was seen in comparison to 4W-
old week and 20W-old. A pronounced neuron loss observed in the drug-treated group may
be attributed to the neurotoxicity of diclofenac sodium (DS) on the developing hippocampal
formation. Age-dependent neuron increase in the CA of 20W-old and neuron decline in GD
of 20W-old control groups may be a result of a dual effect of saline injection during the fetal
life, since these animals were exposed to a stress of 15-day-period of saline injection,
prenatal stress. The reason of no age effect on CA and GD cell number in the drug-treated
groups may be attributed to the depletion of the progenitor cells due to neurotoxicity of DS
in the fetal life of these animals.
© 2006 Elsevier B.V. All rights reserved.
Keywords:
Hippocampus
Nonsteroidal anti-inflammatory
drug
Diclofenac sodium
Stereology
Rat
BRAIN RESEARCH 1127 (2007) 185 – 192
⁎ Corresponding author. Fax: +90 362 312 19 19x2265.
E-mail address: skaplan@omu.edu.tr (S. Kaplan).
0006-8993/$ – see front matter © 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.brainres.2006.10.026
available at www.sciencedirect.com
www.elsevier.com/locate/brainres