Neuroprotection (Acute Phase)

Thyrotropin-Releasing Hormone

Thyrotropin-releasing hormone (TRH) is naturally produced by the hypothalamus. Under normal conditions, it is involved in regulating the release of thyroid stimulating hormone and prolactin. Among individuals with SCI, TRH can take on several functions to remediate secondary injuries such as increasing blood flow, acting as an antioxidant and stabilizing membranes (Fehlings & Baptiste 2005). The exact mechanism of action of this pharmaceutical agent is still unknown. Animal studies examining TRH for acute SCI have found it to contribute to significant long-term motor recovery (Faden et al. 1981a; Faden et al. 1984b), even when the first treatment administration was delayed up to one week (Hashimoto & Fukuda 1991). Animal studies have found that when compared to naloxone and dexamethasone, TRH is significantly more effective than either drug (e.g., Akdemir et al. 1992; Faden et al. 1981b; Faden et al. 1983). In humans, preliminary TRH clinical studies have also been conducted to examine its effect on amyotrophic lateral sclerosis (Brooks et al. 1987).

Author Year

Country

Research Design

PEDro

Sample Size

 Methods Outcomes
Pitts et al. 1995

USA

RCT

PEDro=5

Ninitial=20, Nfinal=17

 Population: Mean age: not specified; Gender: not specified; Level of injury: cervical-lumbar; Severity of injury: complete=35%, incomplete=65%.

Treatment: Patients were randomly assigned to receive either thyrotropin-releasing hormone (TRH; 0.2 mg/kg bolus plus 0.2 mg/kg/h infusion over 6 hr) or placebo within 12 hr of injury.

Outcome Measures: The following after 4 months: motor function, sensory function (pinprick and light touch), severity of neurological recovery using Sunnybrook cord injury scale.

Chronicity: Individuals were entered into the study within 12 hr of sustaining injury.

 Analyses of patients with incomplete injuries:

  1. Patients who received TRH had significantly higher motor functioning compared to patients who received placebo (p=0.043).
  2. Patients who received TRH experienced significantly higher sensory function compared to those who received placebo (p=0.031).
  3. Patients who received TRH had significantly higher Sunnybrook cord injury scores than patients receiving placebo (p=0.044).

Analyses of patients with complete injuries:

  1. There were no significant differences with regards to motor function or sensory function between the two groups (p>0.05).
  2. There were no significant differences with regards to Sunnybrook cord injury between the two groups (p>0.05).

Discussion

In one, small RCT conducted by Pitts et al. (1995), TRH was effective in promoting neurological recovery in patients with incomplete SCI, however not for those with complete SCI. Despite this promising observation, larger clinical trials are required to validate these results.

Conclusion

There is level 1b evidence (from one RCT: Pitts et al. 1995) that thyrotropin-releasing hormone may be effective in promoting neurological recovery in individuals with incomplete acute SCI.

Thyrotropin-releasing hormone may be effective for neurological recovery during the acute phase post SCI in individuals with incomplete injuries.

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