Dexamethasone reduces brain cell apoptosis and inhibits inflammatory response in rats with intracerebral hemorrhage

Abstract

Spontaneous intracerebral hemorrhage (ICH) is associated with high rates of mortality and morbidity. Thus, the identification of novel therapeutic agents for preventing strokes and attenuating poststroke brain damage is crucial. Dexamethasone (DEX) is used clinically to reduce edema formation in patients with spinal cord injury and brain tumors. In this study, we sought to elucidate the effects of DEX treatment on apoptosis and inflammation following ICH in rats. A high dose of DEX (15 mg/kg) was administered immediately following ICH induction and again 3 days later. The inflammatory and apoptotic responses in the rat brains were evaluated by using hematoxylin-eosin, terminal deoxynucleotidyl transferase dUTP nick end labeling, Nissl, and neurofilament-H staining. Levels of phosphorylated neurofilaments and apoptosis-related proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), caspase-3, and P53 were analyzed by Western blotting. This study shows that rats without ICH that received DEX treatment had a fourfold higher expression of Bcl-2 than sham-operated rats. ICH causes an increase in Bax, cleaved caspase-3, and P53 proteins from 4 hr to 7 days following ICH induction. In comparison with the ICH rats, the ICH/DEX rats showed significantly decreased apoptotic cell death and increased neuron survival and maintained neurofilament integrity in the perihematomal region. DEX increased the Bcl-2/Bax ratio and lowered the expression of cleaved caspase-3 at 12 hr and 5 days. The ICH rats were accompanied by activation of the inflammatory response, and DEX treatment modulated the expression of a variety of cell types and then decreased ICH-induced apoptosis.

Time-related morphometric studies of neurofilaments in brain contusions

“…There are also additional data that dexamethasone treatment maintains NF integrity following intracerebral hemorrhage damage [14]. However even with this potential protective influence of dexamethasone authors were able to see significant differences (decrease) in numbers and area fractions of NF between the studied groups.…”

Mechanism and Therapy of Brain Edema after Intracerebral Hemorrhage

“…Patients treated with fingolimod have a higher Glasgow Coma Scale score, lower National Institutes of Health Stroke Scale score, improved neurologic function and fewer ICH-related lung infections without differences in the occurrence of adverse events when compared with the control group. Dexamethasone can promote the recovery of ICH injury by inhibiting the inflammatory response and reduce brain edema because of its capacity to decrease apoptotic cell death and inhibiting the intercellular adhesion molecule-1 and MMP-9 expression [10,84] .…”

“…A similar result was observed in a clinical study [9] . Likewise, dexamethasone can reduce cerebral cell apoptosis and inhibit inflammation [10], and deferoxamine (DFX) provides new therapy target [11] . But before these immunomodulators or other anti-inflammatory agents are used clinically, more experiments are needed.…”

Rapidly calcified all of multiple intracranial hemorrhages occurred in a patient with Chronic idiopathic thrombocytopenic purpura

“…Proliferation of fibroblasts induced formation encapsulation of the hematoma [5]. Lee et al [6] reported that dexamethasone, a synthetic glucocorticoid, reduces brain cell apoptosis and inhibits inflammatory response in rats with intracerebral hemorrhage model. After dexamethasone treatment, neutrophil infiltration is prevented, lymphocytes are present early in the peri-hematoma area, and cell death is inhibited, which may induced several gene expression.…”