The effect of doxycycline on neuron-specific enolase in patients with traumatic brain injury: a randomized controlled trial

Abstract

Objective: We aimed to examine the effect of doxycycline on serum levels of neuron-specific enolase (NSE), a marker of neuronal damage in traumatic brain injury (TBI) patients. Methods: Patients were randomly assigned into two groups ( n = 25 each) to receive either placebo or doxycycline (200 mg daily), with their standard management for 7 days. Results: NSE serum levels in the doxycycline and control groups on day 3 were 14.66 ± 1.78 versus 18.09 ± 4.38 ng/mL, respectively ( p = 0.008), and on day 7 were 12.3 ± 2.0 versus 16.43 ± 3.85 ng/mL, respectively ( p = 0.003). Glasgow Coma Scale (GCS) on day 7 was 11.90 ± 2.83 versus 9.65 ± 3.44 in the doxycycline and control groups, respectively ( p = 0.031). NSE serum levels and GCS scores were negatively correlated ( r = −0.569, p < 0.001). Conclusion: Adjunctive early use of doxycycline might be a novel option that halts the ongoing secondary brain injury in patients with moderate to severe TBI. Future larger clinical trials are warranted to confirm these findings.

The ratio of serum neuron-specific enolase level to admission glasgow coma scale score is associated with diffuse axonal injury in patients with moderate to severe traumatic brain injury

“…Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 ( UCH-L1) will be considered for inclusion in predictive models in expanded studies after they are widely used in routine clinical practice in China. Third, NSE levels are time-dependent factor ( 12 , 35 ), but in our study, the effect of dynamic changes of NSE levels on the 6-month prognosis of moderate to severe TBI was not further evaluated. Fourth, serum of trauma patients with TBI cannot fully reflect the pathological process of brain tissue injury in the early stage, which may bias the hyper-acute assessment.…”

“…Considering the low sensitivity of CT examination for microbleeds and axonal damage caused by DAI in the acute phase ( 32 , 33 ). Additionally, serum NSE is widely used by medical institutions at all trauma treatment centers in China because of its advantages of being easily accessible, low-cost (30–40 RMB), objective, and repeatable ( 12 , 34 , 35 ). We excluded Marshall CT score and combined serum NSE levels within 6 h of injury and admission GCS scores to form a simple, objective, and stable predictor.…”

“…Neuron-specific enolase (NSE) is an isoenzyme of the glycolytic enzyme enolase which exists almost in neuronal cells, with the highest concentrations in the central nervous system. The molecular weight of 78 KD facilitates the leakage of NSE into the extracellular compartment and blood after the structural damage of nerve cells ( 12 ). NSE has been demonstrated to be increased in serum following various types of TBI, making it potentially a sensitive and specific biomarker of neuronal cell damage ( 12 , 13 ).…”

“…The molecular weight of 78 KD facilitates the leakage of NSE into the extracellular compartment and blood after the structural damage of nerve cells ( 12 ). NSE has been demonstrated to be increased in serum following various types of TBI, making it potentially a sensitive and specific biomarker of neuronal cell damage ( 12 , 13 ). However, small cell lung cancers, red blood cells, platelets, adipose tissue, and smooth muscle contain NSE as well ( 14 ).…”

Targets of Neuroprotection and Review of Pharmacological Interventions in Traumatic Brain Injury

“…Another tetracycline derivative, doxycycline, has been investigated in a Phase III clinical trial of moderate to severe TBI (Mansour et al, 2021). Doxycycline administration for the first seven days following injury was associated with a significant reduction in neuron-specific enolase (NSE) level, a biomarker of neuronal damage.…”