Could Early Atorvastatin Offer Anti Inflammatory Effects Upon Brain in Traumatic Head Injury?
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Craniocerebral Trauma; Wounds and Injuries
Study type: Interventional

Summary: 
      3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known as statins, are widely used
      to reduce levels of low-density lipoprotein-cholesterol. As lipid-lowering drugs, statins
      exert neuroprotective effects on ischemic stroke. this study will investigate whether the
      protective effect of statins is mediated by their ability to impact inflammation and oxygen
      free radical levels in cerebral ischemia/reperfusion injury.

      Could Statins affect the neuroinflamation which occurs after traumatic brain injury?
    

Detailed description: 
      Traumatic brain injury (TBI) is one of the most common and financially devastating health
      problems in our society. Once the acute care period has ended, many TBI patients are left
      with motor, cognitive, or emotional dysfunction as a result of their injury. The treatment of
      TBI remains largely supportive, directed toward management of cerebral edema and intracranial
      hypertension via temporizing measures, such as administration of osmotic agents,
      hyperventilation, and ventricular drainage. None of these interventions have been
      definitively demonstrated to improve long-term functional outcome. The failure of preclinical
      therapies to translate into clinical benefit may derive from the heterogeneity of TBI
      pathology, which includes diffuse axonal injury, cerebral contusion, intracerebral hemorrhage
      (ICH), subarachnoid hemorrhage (SAH), and extra parenchymal hemorrhage. These primary insults
      are exacerbated by a secondary neuroinflammatory cascade of cerebral hypoperfusion and
      ischemia, oxidative stress, cerebral edema, and intracranial hypertension. There are a series
      of reactions following cerebral ischemia/reperfusion, such as inflammation and an increase in
      free radicals, which may trigger secondary injury in ischemic tissue. Indeed, the inhibition
      of inflammation reduces tissue damage in ischemia. Thus, understanding the roles of
      inflammation and free radicals in ischemia/reperfusion injury is therefore of great
      importance.

      3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known as statins, are widely used
      to reduce levels of low-density lipoprotein-cholesterol. As lipid-lowering drugs, statins
      exert neuroprotective effects on ischemic stroke. In this study, teh study will investigate
      whether the protective effect of statins is mediated by their ability to impact inflammation
      and oxygen free radical levels in cerebral ischemia/reperfusion injury. Statins have been
      shown to reduce morbidity in patients who did not have high serum cholesterol or
      cardiovascular disease but did have evidence of systemic inflammation. Statins have strong
      efficacy on modulation of inflammatory responses. conditions where statins have been found to
      have a positive effect on disease progression or mortality are primarily dependent on
      leucocyte accumulation. Statins may thus promote the timely resolution of the inflammatory
      response, preventing persistence of inflammation and resultant pathology.

      Magnetic resonance spectroscopy (MRS) allows for measurement of metabolites that are
      undetectable by conventional neuroimaging thereby holding potential to identify traumatic
      brain injury patients that could benefit from specific neuropsychiatric and cognitive
      rehabilitation . Brain energy metabolism is altered after TBI due to posttraumatic
      inflammation and ischemia with mitochondrial dysfunction and loss of neuronal integrity with
      increased cell membrane turnover. MRS is an MRI technique that can detect nuclei with spins
      such as 1H, an abundant by-product of cellular respiration and brain tissue metabolites. As a
      noninvasive and safe technique, MRS is available on clinical MR scanners (1.5 and 3.0 T)
      without ionizing radiation [15]. This method holds the potential to identify compromised
      brain metabolism, but evidence after traumatic brain injury is rare .
    

Intervention name(s): Atorvastatin; placebo
Intervention type(s): Drug; Other
Intervention description(s): will receive 40 mg atrorvastatin 2 days; will receive 40 mg placebo 2 days
Intervention MeSH terms: Atorvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Traumatic brain injury; N-acetyl-aspartate