The Therapeutic Effect of Intranasal Administration of Dexamethasone in Neuroinflammation Induced by Experimental Pulmonary Tuberculosis.
Jacqueline V Lara-EspinosaMaría Fernanda Arce-AcevesDulce Mata-EspinosaJorge Barrios-PayánBrenda Marquina-CastilloRogelio Hernández-PandoPublished in: International journal of molecular sciences (2021)
Tuberculosis (TB) is an important infectious disease and a public health problem. The organs most frequently affected by TB are the lungs; despite this, it has been reported that TB patients suffer from depression and anxiety, which have been attributed to social factors. In previous experimental work, we observed that the extensive pulmonary inflammation characteristic of TB with high cytokine production induces neuroinflammation, neuronal death and behavioral abnormalities in the absence of brain infection. The objective of the present work was to reduce this neuroinflammation and avoid the psycho-affective disorders showed during pulmonary TB. Glucocorticoids (GCs) are the first-line treatment for neuroinflammation; however, their systemic administration generates various side effects, mostly aggravating pulmonary TB due to immunosuppression of cellular immunity. Intranasal administration is a route that allows drugs to be released directly in the brain through the olfactory nerve, reducing their doses and side effects. In the present work, dexamethasone's (DEX) intranasal administration was evaluated in TB BALB /c mice comparing three different doses (0.05, 0.25 and 2.5 mg/kg BW) on lung disease evolution, neuroinflammation and behavioral alterations. Low doses of dexamethasone significantly decreased neuroinflammation, improving behavioral status without aggravating lung disease.
Keyphrases
- mycobacterium tuberculosis
- pulmonary tuberculosis
- cerebral ischemia
- lipopolysaccharide induced
- lps induced
- traumatic brain injury
- cognitive impairment
- public health
- pulmonary hypertension
- high dose
- low dose
- subarachnoid hemorrhage
- inflammatory response
- end stage renal disease
- blood brain barrier
- white matter
- chronic kidney disease
- infectious diseases
- metabolic syndrome
- mental health
- hepatitis c virus
- patient reported outcomes
- functional connectivity
- hiv infected
- electronic health record
- antiretroviral therapy