The effects of systemically administered methylprednisolone and recombinant human erythropoietin after acute spinal cord compressive injury in rats

Abstract

The study design was to decrease the damage of spinal cord on the experimentally induced acute spinal cord injury in rats. The objective of this study was to evaluate whether recombinant human erythropoietin (rHu-EPO) and methylprednisolone (MPSS) improve neurological function and histopathological changes if systemically administered after traumatic spinal cord injury. This study included 48 rats that underwent experimental SCI. Forty-eight animals were randomly divided into six groups. Animals constituted a moderate compression of 0.6 N that was produced by application of an aneurysm clip at level T3 for 1 min. rHu-EPO (1,000 and 3,000 U (Unit) per kg of body weight i.p.) and MPSS (30 mg/kg) were administered 5 min after injury, and control group was saline treated. (1) Control group (n=8), (2) MPSS group (n=8), (3) rHu-EPO 1,000 U group (n=8), (4) MPSS + rHu-EPO 1,000 U group (n=8), (5) rHu-EPO 3,000 U group (n=8), and (6) MPSS + rHu-EPO 3,000 U group (n=8). The neurological function and histopathology were evaluated at 24 and 72 h. According to the neurological functional test scores significant improvements between the control group and the other groups that had taken medical treatment were observed (P<0.001). Histopathologically severe ischemic findings were observed in the control group. A significant decrease in ischemic damage was detected in MPSS + rHu-EPO 3,000 U group (P<0.001). The most significant neurological functional and histopathological improvements were observed after systemical administration of MPSS + rHu-EPO 3,000 U and rHu-EPO 3,000 U. Furthermore, the MPSS + rHu-EPO 3,000 U group provides the most improved neurological functional and histopathological recovery.

Erythropoietin in spinal cord injury

“…Yet, it is also supported that such dismission of transaction models is inappropriate because these models allow a much clearer analysis of the cellular effects of trauma, and also of the effects of the potential therapies, since they are much less complex. Compression is carried out by means of a modified aneurismal clip, forceps or applying weight on exposed SC [4,19,36]. Contusion is caused by either displacing SC or hitting it with a dropped weight (steel rod) and is characterized by more extensive damage [11,33,37,43,62,74,75].…”

“…The aforementioned problems are surpassed with the administration of exogenous rhEPO which has been suggested to produce substantial neuroprotection in animal models of traumatic SCI [4,11,19,33,36,37,39,43,44,62,74,75], spinal nerve root crush injury [66], transient SC ischemia [18,68], and SC inflammation in EAE [1]. The principal findings of the above studies are shown in Table 1.…”

Regulation of Inflammatory Cytokines for Spinal Cord Injury Repair Through Local Delivery of Therapeutic Agents

“…EPO was first reported to dramatically improve functional neurological status in a rabbit ischemia SCI model 11. This kind of functional recovery was also demonstrated in rat,17, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96 mouse,86, 97 pig,22 and other rabbit98 models.…”

Point of View about Erythropoietin in Treatment of Central Nervous System Diseases

“…Many previous studies have shown that erythropoietin (EPO) inhibits oxidative stress and glutamate release [1,2], regulates inflammation [3], decreases lipid peroxidation [2] and increases blood flow and tissue oxygenation [4] and nitric oxide production [5,6] in various animal models. EPO is a glycoprotein cytokine which is produced mainly by the fetal liver and adult kidney and involved in regulation of red blood cell production.…”