Evaluation of the effects of erythropoietin and interleukin-6 in rats submitted to acute spinal cord injury

Abstract

OBJECTIVE: To evaluate the effects of interleukin-6 (IL-6) and erythropoietin (EPO) in experimental acute spinal cord injury (SCI) in rats. METHODS: Using standardized equipment, namely, a New York University (NYU) Impactor, a SCI was produced in 50 Wistar rats using a 10-g weight drop from a 12.5-mm height. The rats were divided into the following 5 groups of 10 animals each: “Group EPO”, treated with erythropoietin only; “Group EPO + IL-6”, treated with both substances; “Group IL-6”, receiving IL-6 administration only; “Group Placebo”, receiving a placebo solution; and “Group Sham”, submitted to an incomplete procedure (only laminectomy, without SCI). All drugs and the placebo solution were administered intraperitoneally for three weeks. The animals were followed up for 42 days. Functional motor recovery was monitored by the Basso, Beattie, and Bresnahan (BBB) scale on days 2, 7, 14, 21, 28, 35 and 42. Motor-evoked potential tests were performed on the 42nd day. Histological analysis was performed after euthanasia. RESULTS: The group receiving EPO exhibited superior functional motor results on the BBB scale. IL-6 administration alone was not superior to the placebo treatment, and the IL-6 combination with EPO yielded worse results than did EPO alone. CONCLUSIONS: Using EPO after acute SCI in rats yielded benefits in functional recovery. The combination of EPO and IL-6 showed benefits, but with inferior results compared to those of isolated EPO; moreover, isolated use of IL-6 resulted in no benefit.

Neurological recovery and antioxidant effect of erythropoietin for spinal cord injury: A systematic review and meta-analysis

“…The meta-analysis indicated that SCI rats receiving EPO therapy showed a significant locomotor function recovery in all studies (1 d to 28 d, P < 0.01; Figure 2 ). After the intervention of EPO, the BBBs score increased [1 d, 21 studies ( 18 , 25 , 35 – 37 , 41 , 43 – 46 , 48 , 49 , 51 , 54 , 59 , 61 , 63 – 65 ), WMD = 0.69, 95% CI [0.22, 1.15], P = 0.004; 3 d, 17 studies ( 18 , 25 , 35 , 42 , 43 , 46 , 48 , 49 , 58 , 63 , 66 – 70 ), WMD = 2.50, 95% CI [1.69, 3.31], P < 0.00001; 7 d, 24 studies ( 18 , 25 , 35 , 36 , 42 , 43 , 45 , 46 , 48 , 49 , 54 , 58 , 59 , 63 , 65 , 67 – 69 , 71 – 74 ), WMD = 3.31, 95% CI [2.21, 4.41], P < 0.00001; 14 d, 20 studies ( 18 , 25 , 35 , 42 , 43 , 45 , 46 , 48 , 49 , 58 , 59 , 63 , 65 , 67 – 69 , 73 , 74 ), WMD = 3.80, ...…”

“…Subgroup analysis was carried out according to the different animal models and species, as well as the different EPO administration. While, there was no difference between different animal models and species, then the subgroup analysis recommended 5,000 UI/kg is the more effective dose [7 d, 11 studies ( 18 , 35 , 36 , 41 , 44 , 45 , 54 , 59 , 61 , 64 , 65 ), WMD = 4.05, 95% CI (2.23, 5.88), P < 0.0001; Table 3 ], although its effect was not statistically different from that of 1,000 UI/kg [7 d, nine studies ( 18 , 25 , 43 , 45 , 46 , 48 , 49 , 51 , 63 ), WMD = 3.13, 95% CI (1.05, 5.21), P = 0.003; Table 3 ]. Then, the different administration methods of animals, single or multiple administration after SCI dis not affect the neuroprotective effect of EPO for SCI (Table 3 ).…”

Construction of the gene network in the spinal cord injury treated by coptidis rhizoma based on network pharmacological and molecular docking

“…Body stress response, tissue damage, or inflammation can elevate the level of IL-6. Studies have shown that serum IL-6 increases after burning, amputation, and closed injury in mice (Barros AGC, et al, 2019). Apoptosis is a type of programmed cell death.…”

Insulin‑like growth factor 1 promotes neurological functional recovery after spinal cord injury through inhibition of autophagy via the PI3K/Akt/mTOR signaling pathway

“…A 10-g rod was freely dropped from a height of 25 mm, which was controlled by an NYU Impactor II (New York University Medical Center, New York, NY, USA), to impact the T10 segment of the spinal cord; wagging tail reflex and lower limb spasms were observed. Laminectomy was performed on the rats in the sham group without SCI ( 35 ). The wound was sutured layer by layer.…”