Galantamine protects against synaptic, axonal, and vision deficits in experimental neurotrauma

Abstract

Our goal was to investigate the neuroprotective effects of galantamine in a mouse model of blast-induced indirect traumatic optic neuropathy (bITON). Galantamine is an FDA-approved acetylcholinesterase inhibitor used to treat mild-moderate Alzheimer’s disease. We exposed one eye of an anesthetized mouse to repeat bursts of over-pressurized air to induce traumatic optic neuropathy. Mice were given regular or galantamine-containing water (120 mg/L) ad libitum, beginning immediately after blast and continuing for one month. Electroretinograms and visual evoked potentials were performed just prior to endpoint collection. Histological and biochemical assessments were performed to assess activation of sterile inflammation, axon degeneration, and synaptic changes. Galantamine treatment mitigated visual function deficits induced by our bITON model via preservation of the b-wave of the electroretinogram and the N1 of the visual evoked potential. We also observed a reduction in axon degeneration in the optic nerve as well as decreased rod bipolar cell dendritic retraction. Galantamine also showed anti-inflammatory and antioxidant effects. Galantamine may be a promising treatment for blast-induced indirect traumatic optic neuropathy as well as other optic neuropathies.

A Novel Galantamine-Curcumin Hybrid as a Potential Multi-Target Agent against Neurodegenerative Disorders

“…GAL has an antioxidant activity related with the enolic OH group [ 6 ]. One of the mechanisms by which GAL improves the mental function in Alzheimer’s dementia is thought to be its antioxidant effect [ 55 , 56 , 57 ]. CU also is a proven antioxidant and brain protector [ 58 , 59 , 60 ].…”

Visual Outcomes in Experimental Rodent Models of Blast-Mediated Traumatic Brain Injury

“…Of these, 75% (9) reduced inflammation, 33.33% (4) reduced apoptotic pathways, 25% (3) reduced oxidative stress levels, 8.33% (1) decreased excitotoxicity, and 8.33% (1) reduced tryptophan oxidative degradation. Galantamine, an acetylcholinesterase inhibitor, blocked inflammation, oxidative stress, and excitotoxicity (Naguib et al, 2020). Inflammation was blocked with cannabinoid type-2 receptor inverse agonists, raloxifene (Honig et al, 2019) and SMM-189 (Reiner et al, 2014;Guley et al, 2019) the paracrine factors secreted by adipose stem cell concentrated conditioned media (ASC-CCM) pre-stimulated with inflammatory cytokines (Honig et al, 2019) and interleukin-1 receptor (IL-1RI) antagonist anakinra (Evans et al, 2020).…”

“…Optic nerve degeneration in blast-injured mice was consistently identified (Petras et al, 1997;Mohan et al, 2013;Bricker-Anthony et al, 2014a,b, 2016Bernardo-Colon et al, 2018Guley et al, 2019;Honig et al, 2019;Vest et al, 2019;Evans et al, 2020;Naguib et al, 2020). The optic nerve was protected pharmacologically with anakinra (Evans et al, 2020), EPO (Bricker-Anthony et al, 2017), raloxifene (Honig et al, 2019), SMM-189 (Reiner et al, 2014;Guley et al, 2019), and galantamine (Naguib et al, 2020) along with dietary changes such as vitamin E supplements and a ketogenic diet (Bernardo-Colon et al, 2018).…”

“…SMM-189 (Guley et al, 2019) and raloxifene (Honig et al, 2019) may prevent secondary neuroinflammation in the optic nerve. Similarly, galantamine treatment (Naguib et al, 2020), sufficient levels of vitamin C, vitamin E, and a ketogenic diet (Bernardo-Colon et al, 2018) may protect against optic nerve degeneration by decreasing the presence of ROS and the subsequent upregulation of inflammatory cytokines.…”

Antioxidant Activity of a Novel Acetylcholinesterase Inhibitor: In Vivo and Ex vivo Studies

“…GAL has an antioxidant activity related with the enolic OH group [6]. One of the mechanisms by which GAL improves the mental function in Alzheimer's dementia is thought to be its antioxidant effect [49][50][51]. CU also is a proven antioxidant and brain protector [52][53][54].…”