Research Article: The effect of rosmarinic acid on deformities occurring in brain tissue by craniectomy method. Histopathological evaluation of IBA-1 and GFAP expressions 1

Date Published: June 19, 2020

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em

Author(s): Hüseyin Özevren, Engin Deveci, Mehmet Cudi Tuncer.


To investigate the role of Rosmarinic acid (RA) in the prevention of
traumatic brain injury and the immunohistochemical analysis of IBA-1 and
GFAP expressions.

Healthy male rats were randomly divided into 3 groups consisting of 10 rats.
Groups were as follows; control group, traumatic brain injury (TBI) group,
and TBI+RA group. After traumatic brain injury, blood samples were taken
from the animals and analyzed with various biochemical markers. And then
IBA-1 and GFAP expressions were evaluated immunohistochemically.

Significant results were obtained in all biochemical parameters between
groups. Immunohistochemical sections showed IBA-1 not only in microglia and
macrophage activity but also in degenerative neurons in blood vessel
endothelial cells. However, GFAP reaction and post-traumatic rosmarinic acid
administration showed positive expression in astrocytes with regular
structure around the blood vessel.

Rosmarinic acid in blood vessel endothelial cells showed that preserving the
integrity of astrocytic structure in the blood brain barrier may be an
important antioxidant.

Partial Text

Traumatic brain injury is a health problem known as the cause of mortality and
disability in young people. Primary and secondary injury cascades that cause delayed
neuronal dysfunction, synapse loss and cell death are associated with traumatic
brain injury 1 , 2 . Secondary damage develops within minutes to days following the primary
insult, release of the inflammatory mediators, formation of the free radicals,
excessive release of the neurotransmitters (glutamate and aspartate), influx of
calcium and sodium ions into neurons, and dysfunction of mitochondria 3 .

All techniques performed in this examination were approved by the Ethics Committee
for Animal Experimentation of the Faculty of Medicine at Dicle University, Turkey.
Male Sprague Dawley rats (280–310 g) were housed in an air-conditioned room with
12-h light and dark cycles, where the temperature (23±2°C) and relative humidity
(65–70%) were kept constant. All rats at the end of experiment were healthy and no
difference in food/water consumption and body weight gain between experimental and
control rats were observed.

Traumatic brain injury often promotes disruption of the blood-brain barrier integrity
and the neurovascular unit, which can result in vascular leakage, edema, hemorrhage,
and hypoxia. Other pathologic mechanisms include cell death within the meninges and
brain parenchyma, stretching and tearing of axonal fibers, and disruptions at the
junctions between white and gray matter, stemming from rotational forces that cause
shearing injuries 24 . Previous studies have shown that a variety of pathological factors, such as
oxidative stress, inflammatory response and apoptosis, are involved in secondary
brain injury after traumatic brain injury. Furthermore, early interventions to
reduce the level of oxidative stress and the extent of the inflammatory response can
significantly reduce the extent of traumatic brain injury 25 . Özevren et al . 26 found enlarged blood vessels, bleeding and swelling after traumatic injury in
the brain. In addition, nuclei of the neurons were dissociated and vacuolar
degeneration was observed. Furthermore, early interventions to reduce the level of
oxidative stress and the extent of the inflammatory response can significantly
reduce the extent of TBI 17 .

Despite the results, there are a few limitations in the clinical contribution.
Especially after trauma, GFAP increases in intermediate filaments in astrocytes with
the development of astrocytosis in the infection or neurodegenerative process and
induction in the signal pathway in the astrocytes. Due to the antioxidative effect
of rosmarinic acid, it was thought that it may regulate this protein increase in
astrocyte regulation. TBI caused cell apoptosis, microglial activation and an
inflammatory response. The weakening of microglial activation, Iba-1, an important
biomarker for microglial activation, is thought to have its expression
down-regulated, but the positive Iba-1 activity with the effect of rosmarinic acid
is important to balance microglia activation.




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