The Therapeutic Effect of Intranasal Administration of Dexamethasone in Neuroinflammation Induced by Experimental Pulmonary Tuberculosis

Abstract

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.

Effect of Curcumin in Experimental Pulmonary Tuberculosis: Antimycobacterial Activity in the Lungs and Anti-Inflammatory Effect in the Brain

“…A mouse model of progressive pulmonary TB has previously been reported [47,97,98]. The reference Mtb strain H37Rv was grown in a 7H9 medium enriched with OADC.…”

“…Four homogenate dilutions were spread onto Bacto Middlebrook 7H10 agar supplemented with OADC on triplicate plates. CFU count was performed over 21 days of incubation at 37 • C and 5% CO 2 [47,57].…”

“…The approach for conducting behavior tests in the mouse model of progressive lung TB was previously reported [47,57]. Animals were exposed to the test environment 24 h before it was performed.…”

“…Infected mice's motor function and reflexes were assessed using a modified neurologic severity score (NSS) [105] and have been reported elsewhere [47,57]. These modifications included assessments to test the animals' senses.…”

“…In diseases with an inflammatory component, first-line medications have traditionally been agents that reduce inflammation [47]. Curcumin (CUR) or diferuloylmethane (1, 7-bis (4-hydroxy-3-methoxyphenol)-1, 6-heptadiene-3, 5-dione) is a polyphenolic compound obtained from the rhizomes of Curcuma longa [48,49], a rhizomatous native plant from South and Southeast Asia that belongs to the family Zingiberaceae [50].…”