Introduction
Recent evidence shows that hippocampal pyramidal cells are low in patients with status epilepticus [9] and glial cells and neuro-inflammation are involved in the pathogenesis of epilepsy; therefore, it is hopeful that by targeting these cells, the existing therapeutic strategies can be completed. Recent studies have shown different functions of microglia in the development and maintenance of the central nervous system (CNS) in both healthy people and patients. The treatment of hippocampal tissue and the cerebral cortex with compounds that induce seizures indicate the direct stimulation of astrocytes through a pathway that causes the release of glutamate from glial cells. Anticonvulsant drugs can reduce the activity of this non-neuronal pathway [2]. When these stimulatory pathways are considered together with GABA- and adenosine-dependent inhibition in reactive astrocytes, the role of these supporting cells in causing seizures become more evident. Therefore, the dysfunction of astrocytes in the regulatory feedback loop is one of the causes of seizures. 
Prolactin is a hormone with different actions in the CNS that causes the activation and suppression of microglia and astrocytes release inflammatory and anti-inflammatory cytokines [3]. Prolactin performs different actions through its receptors, which are found both in both nerve and glial cells of the brain. Considering the dynamics of glial cells and their function in different pathological conditions, as well as the protective effect of prolactin in nerve cells, there is a possibility that prolactin can be a new target in the neuropathology of neurological diseases [4]. Therefore, the purpose of this study is to compare the effects of cabergoline and levetiracetam on tissue and stereological changes in the cortex, hippocampus and cerebellum.
Methods
In the present study, 30 adult female rats were randomly divided into five groups of 6 including control (normal saline, oral gavage), chronic seizure (30 mg/kg Pentylenetetrazole, i.p., three times a week for 10 consecutive weeks) [5], chronic seizure+levetiracetam (30 mg/kg Pentylenetetrazole+50 mg/kg levetiracetam, oral gavage( [6], chronic seizure+cabergoline (30 mg/kg Pentylenetetrazole+0.05 mg/kg cabergoline, oral gavage) [7] and chronic seizure+levetiracetam+cabergoline (30 mg/kg Pentylenetetrazole+25 mg/kg levetiracetam+0.025 mg/kg cabergoline). The animals were anesthetized with ketamine-xylazine and their brain tissue was removed and placed in a 10% formalin solution for histological and stereological studies [8]. After fixing the samples in three areas such as the hippocampus, cerebellum, and cerebral cortex, the tissue samples underwent standard procedures, including dehydration, clarification, and impregnation with paraffin. Using a rotary microtome, thin tissue slices with a thickness of 5 micrometers for histological study and a thickness of 50 micrometers for stereological study were created [9].
Results
The numbers of neurons and neuroglia in the cerebral cortex and in the molecular and granular layers of the cerebellum in the treatment groups were not significantly different from those in the control group. The number of neurons in the Purkinje layer of the cerebellum does was not significantly different compared to that in the control group. The number of neurons and neuroglia in CA1, CA2 and CA3 regions of the hippocampus in the seizure group significantly decreased compared to the control group. In the dentate gyrus located in the hippocampus, the number of neurons in all treatment groups and the number of neuroglia in the seizure group were significantly reduced compared to the control group. Levetiracetam and cabergoline alone could relatively improve this decrease, while their simultaneous use had a more favorable effect (Figure 1).  The results of histological studies on the cerebral cortex, cerebellum, and hippocampus showed that the tissue structure as well as the condition and distribution of neurons and neuroglia in the cerebral cortex and cerebellum were normal in all groups, and no lesion or tissue damage was observed. 
The results of the tissue studies related to the hippocampus shows no determined damage in different areas of the hippocampus
Discussion 
In healthy brains, astrocytes exert appropriate feedback control for the regulation of neuronal activities. In epileptic brains, they regulate the expression level of neuronal NMDA receptors and involve in their stimulation by releasing glutamate and D-serine. Prolactin is a hormone that has a dual role in nerve cells; finding its connection in the pathways of nerve failure can be useful. It seems that the increase of prolactin after seizure has a protective role in the occurrence of epileptic activities. Prolactin both activates and suppresses microglia and astrocytes, and causes the release of inflammatory and anti-inflammatory cytokines. Previous studies have found glial cells to be effective in the pathogenesis of epilepsy, and it is hopeful that by targeting them, their role in this process can be found more effectively [10]. In healthy brains, astrocytes exert appropriate feedback control in the regulation of neuronal activity and play an important role in maintaining the normal level of synchronization. In epileptic brains, they regulate the surface expression of neuronal NMDA receptors and participate in their stimulation by releasing glutamate and d-serine. So it can be concluded that prolactin is a hormone that has a dual role in nerve cells, so finding its connection in the pathways of nerve failure can be important.Therefore, the possibility that the increase of prolactin after convulsive activities has a protective role in the occurrence of epileptic activities is not far from expected

Ethical Considerations
Compliance with ethical guidelines
This study was approved by the biomedical ethics committee of the University of Tabriz. 

Funding
This study was funded by the University of Tabriz.

Authors' contributions
Conceptualization, design, data acquisition and interpretation, funding acquisition, supervision: Yousef Panahi; preparing initial draft: Yousef Panahi and Mohammad Hossein Hajati Pishvari; editing & review, data analysis: Gholamreza Hamidian. 

Conflicts of interest
The authors declared no conflict of interest. 

Acknowledgements
The authors would like to thank the physiology unit of the Faculty of Veterinary Medicine at the University of Tabriz, including Gholamreza Vafaei Saiah, for their cooperation in using their laboratory facilities.


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