J Korean Neurosurg Soc.  2013 Jul;54(1):1-7. 10.3340/jkns.2013.54.1.1.

Neuroprotective Effects of Quetiapine on Neuronal Apoptosis Following Experimental Transient Focal Cerebral Ischemia in Rats

• Yilmaz MB
• Tonge M
• Emmez H
• Kaymaz F
• Kaymaz M

• KMID: 2190849
• DOI: http://doi.org/10.3340/jkns.2013.54.1.1

Abstract

OBJECTIVE
This study was undertaken in the belief that the atypical antipsychotic drug quetiapine could prevent apoptosis in the penumbra region following ischemia, taking into account findings that show 5-hydroxytryptamine-2 receptor blockers can prevent apoptosis.
METHODS
We created 5 groups, each containing 6 animals. Nothing was done on the K-I group used for comparisons with the other groups to make sure adequate ischemia had been achieved. The K-II group was sacrificed on the 1st day after transient focal cerebral ischemia and the K-III group on the 3rd day. The D-I group was administered quetiapine following ischemia and sacrificed on the 1st day while the D-II group was administered quetiapine every day following the ischemia and sacrificed on the 3rd day. The samples were stained with the immunochemical TUNEL method and the number of apoptotic cells were counted.
RESULTS
There was a significant difference between the first and third day control groups (K-II/K-III : p=0.004) and this indicates that apoptotic cell death increases with time. This increase was not encountered in the drug groups (D-I/D-II : p=1.00). Statistical analysis of immunohistochemical data revealed that quetiapine decreased the apoptotic cell death that normally increased with time.
CONCLUSION
Quetiapine is already in clinical use and is a safe drug, in contrast to many substances that are used to prevent ischemia and are not normally used clinically. Our results and the literature data indicate that quetiapine could help both as a neuronal protector and to resolve neuropsychiatric problems caused by the ischemia in cerebral ischemia cases.

Keyword

Quetiapine; Neuronal apoptosis; Neuroprotective; Transient focal cerebral ischemia

MeSH Terms

Animals
Apoptosis
Brain Ischemia
Cell Death
Dibenzothiazepines
In Situ Nick-End Labeling
Ischemia
Neurons
Neuroprotective Agents
Rats
Quetiapine Fumarate
Dibenzothiazepines
Neuroprotective Agents

Figure

• 

  Fig. 1 A : Neuron with brown marking following ApopTag staining in the K-II group. The black arrow shows an apoptotic cell sample (original magnification 40×). B : Neuron marked brown after ApopTag staining in the K-III group. The ApopTag (+) neurons are seen to be denser in the K-II group. The black arrow shows an apoptotic cell (original magnification 40×).

• 

  Fig. 2 A : Normal cells stained with methyl green and ApopTag (+) neurons stained brown in the D-I group (original magnification 40×). B : Normal cells stained with methyl green (blue arrow) are seen among the ApopTag (+) cells (black arrow) in the D-II group ischemic area (original magnification 40×). Significant apoptotic cell increase is not visible in D-I and D-II groups.

• 

  Fig. 3 Graphical view of median apoptotic cell counts detected in each group.

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