Methamphetamine exacerbates pathophysiology of traumatic brain injury at high altitude. Neuroprotective effects of nanodelivery of a potent antioxidant compound H-290/51

Hari Shanker Sharma*, José Vicente Lafuente, Lianyuan Feng, Dafin F. Muresanu, Preeti K. Menon, Rudy J. Castellani, Ala Nozari, Seaab Sahib, Z. Ryan Tian, Anca D. Buzoianu, Per Ove Sjöquist, Ranjana Patnaik, Lars Wiklund, Aruna Sharma

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Military personnel are often exposed to high altitude (HA, ca. 4500–5000 m) for combat operations associated with neurological dysfunctions. HA is a severe stressful situation and people frequently use methamphetamine (METH) or other psychostimulants to cope stress. Since military personnel are prone to different kinds of traumatic brain injury (TBI), in this review we discuss possible effects of METH on concussive head injury (CHI) at HA based on our own observations. METH exposure at HA exacerbates pathophysiology of CHI as compared to normobaric laboratory environment comparable to sea level. Increased blood-brain barrier (BBB) breakdown, edema formation and reductions in the cerebral blood flow (CBF) following CHI were exacerbated by METH intoxication at HA. Damage to cerebral microvasculature and expression of beta catenin was also exacerbated following CHI in METH treated group at HA. TiO2-nanowired delivery of H-290/51 (150 mg/kg, i.p.), a potent chain-breaking antioxidant significantly enhanced CBF and reduced BBB breakdown, edema formation, beta catenin expression and brain pathology in METH exposed rats after CHI at HA. These observations are the first to point out that METH exposure in CHI exacerbated brain pathology at HA and this appears to be related with greater production of oxidative stress induced brain pathology, not reported earlier.

Original languageEnglish (US)
Title of host publicationProgress in Brain Research
PublisherElsevier B.V.
DOIs
StateAccepted/In press - 2021
Externally publishedYes

Publication series

NameProgress in Brain Research
ISSN (Print)0079-6123
ISSN (Electronic)1875-7855

Keywords

  • Antioxidant
  • Brain edema
  • Brain pathology
  • Cerebral blood flow
  • H-290/51
  • High altitude
  • Methamphetamine
  • Military medicine
  • Nanowired delivery
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)

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