Nicotine exacerbates brain edema during in vitro and in vivo focal ischemic conditions.
We have previously shown that nicotine, the addictive component of tobacco products, alters the blood-brain barrier (BBB) Na(+),K(+),2Cl(-) cotransporter (NKCC) during in vitro hypoxia-aglycemia exposure. Attenuation of abluminal NKCC suggests that accumulation of ions in the brain extracellular fluid would result in an increase of fluid or cytotoxic edema in the brain during hypoxia-aglycemia or stroke conditions. To further investigate whether nicotine products have the potential to worsen stroke outcome by increasing edema formation, two separate models to mimic stroke conditions were utilized to decipher the effects of short-term and long-term administrations of nicotine products on brain edema following stroke. Oxygen glucose deprivation (OGD) was studied in rat hippocampal slices with short-term or long-term exposure to nicotine and cigarette smoke constituents. During short-term exposure, the presence of nicotine at a concentration mimicking heavy smokers increased water content of hippocampal slices during OGD. Furthermore, long-term 1-week administration of nicotine increased water content in hippocampal slices that could be attenuated with nicotine acetylcholine receptor (nAChR) antagonists, suggesting nicotine increase edema during OGD via nAChRs. A second model of focal ischemia, middle cerebral artery occlusion, showed an increase of infarct size during short-term exposure to nicotine and an increase of edema during both short-term and long-term administration of nicotine, compared with saline controls. These findings support the paradigm that nicotine products not only increase the incidence of stroke but also have the potential to worsen stroke outcome by increased edema formation.
Paulson
Jennifer R
JR
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University, Health Sciences Center, Amarillo, Texas, USA.
Yang
Tianzhi
T
Selvaraj
Pradeep K
PK
Mdzinarishvili
Alexander
A
Van der Schyf
Cornelis J
CJ
Klein
Jochen
J
Bickel
Ulrich
U
Abbruscato
Thomas J
TJ
D000818:Animals; D001784:Blood Gas Analysis; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001929:Brain Edema / Q000097:blood / Q000473:pathology*; D020520:Brain Infarction / Q000097:blood / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007003:Hypoglycemia / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000097:blood / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000009:adverse effects; D062789:Tobacco Products
D012906:Smoke; D009538:Nicotine