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Transfection of parasympathetic ganglionic neurons with AAV2‐nNOScDNA protects rat brain from stroke
Author(s) -
Talman William T.,
Easker David,
Dragon Deidre Nitschke,
Lin LiHsien
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.604.13
Subject(s) - medicine , stroke (engine) , forebrain , saline , anesthesia , stimulation , middle cerebral artery , endocrinology , central nervous system , ischemia , mechanical engineering , engineering
Previous studies show that interruption of parasympathetic nerves from the pterygopalatine ganglion (PPG) increases stroke size, while electrical stimulation reduces it in an animal model. Because nitric oxide (NO) is a putative transmitter of those nerves we hypothesized that upregulating neuronal NO synthase (nNOS) in the PPG will protect brain during permanent occlusion of the middle cerebral artery (MCAO). In anesthetized rats, we injected vehicle (phosphate buffered saline, PBS; N= 8), adeno‐associated virus type 2 vector (AAV2) with enhanced green fluorescent protein (AAV2‐eGFP; N= 10), or AAV2 with nNOScDNA (AAV2‐nNOScDNA, N = 9) into the PPG 8 to 13 days prior to MCAO. In 16 additional animals no injection was made into the PPG prior to MCAO. Animals were evaluated for clinical signs of stroke and euthanized 24 hours after MCAO. Sections of forebrain were stained with 2,3,5 triphenyltetrazolium chloride and analyzed with ImageJ to quantify stroke areas. Infarcts in untreated control animals involved 37 ± 1 % (mean ± SEM) of the brain at the level of the MCA. Infarct size in animals treated with PBS or with AAV2‐eGFP was 34 ± 2% and 33 ± 2% respectively. In animals treated with AAV2‐nNOScDNA infarcts were significantly smaller (24 ± 4 %) than in each of the other groups. Therefore, upregulation of nNOS in PPG may protect the brain from ischemic injury. Support: VA Merit Review, NIH R01 HL59593 and R01 HL088090.