Therapeutic Effect of Nicotine in a Mouse Model of Intracerebral Hemorrhage

Abstract

Intracerebral hemorrhage (ICH) resulting from the leakage of blood into the brain parenchyma triggers severe tissue damage involving neurodegeneration and inflammation. Increasing lines of evidence indicate that the stimulation of central nicotinic acetylcholine receptors affords neuroprotection against various insults and also suppresses the proinflammatory activation of microglia. Therefore, the present study aimed to determine whether the administration of nicotine modifies the pathological consequences of ICH, using a mouse model of ICH induced by intrastriatal injection of collagenase. Daily intraperitoneal administration of nicotine (2 mg/kg), starting from 3 h after the induction of ICH, inhibited apoptosis and decreased the number of remaining striatal neurons at 3 days after the insult. We also found that nicotine administration increased the relative expression level of the antiapoptotic protein B cell lymphoma-2 versus that of the proapoptotic protein Bax in the brain. In addition, nicotine administration attenuated the activation of microglia/macrophages, infiltration of neutrophils, and increases in oxidative stress associated with ICH, without affecting hematoma expansion and brain edema. It is noteworthy that mice treated with nicotine exhibited improved sensorimotor performance and a marked increase in survival rate after ICH. These results indicate that nicotinic acetylcholine receptors may serve as a novel target for emergency therapy for ICH.

Scavenger receptor SRA attenuates microglia activation and protects neuroinflammatory injury in intracerebral hemorrhage

“…Emerging evidence suggests that inflammatory mechanisms are involved in the progression of ICH-induced brain injury (Jwa et al, 2011;Sansing et al, 2011;Hijioka et al, 2011). Inflammation is mediated by cellular components, such as leukocytes and microglia, and molecular components, including prostaglandins, chemokines, cytokines, extracellular proteases, and reactive oxygen species (Moxon-Emre and Schlichter, 2011;Loftspring et al, 2011;Wu et al, 2011).…”

In vivo imaging of Α7 nicotinic receptors as a novel method to monitor neuroinflammation after cerebral ischemia

“…Furthermore, α7 receptors have been involved in some brain disorders including schizophrenia (Young & Geyer, ), Alzheimer's disease (Hernandez & Dineley, ), bipolar disorders (Thomsen, Weyn, & Mikkelsen, ) and traumatic brain injury (Verbois, Scheff, & Pauly, ). Likewise, the stimulation of α7 nAChRs protects neurons from insults associated with neurodegenerative disorders (Mudo, Belluardo, & Fuxe, ), ischemic damage (Shimohama et al, ) and intracerebral hemorrhage (Hijioka, Matsushita, Hisatsune, Isohama, & Katsuki, ). The protective effect of these receptors in brain pathologies has been related to the suppression of inflammation through the modulation of immune cells by the cholinergic anti‐inflammatory pathway (de Jonge & Ulloa, ; Wang et al, ), however, the mechanisms involved are not well understood.…”

Intracerebral hemorrhage in mouse models: therapeutic interventions and functional recovery

“…Collagenase induced ICH mice treated with daily administration of nicotine at 2 mg/kg IP, with first dose 3 h after ICH showed reduced activation of microglia/macrophages in the perihematomal areas and increased Striatal neuron survival associated with an increased expression of the antiapoptotic protein B cell lymphoma-2. In addition, the nicotine treated mice showed improved sensorimotor performance assessed on beam-walking, modified limb-placing and adhesive removal test with improved overall survival rate (Hijioka et al 2011). Similar effects are seen with ICH mice treated with a direct α7 nAChR agonist (Hijioka et al 2012).…”