title: Administration of Huperzia quadrifariata Extract, a Cholinesterase Inhibitory Alkaloid Mixture, has Neuroprotective Effects in a Rat Model of Cerebral Hypoxia-Ischemia.
abstract: Neonatal hypoxia-ischemia (HI) is an etiologic component of several neurologic pathologies associated to cognitive impairment. The mechanisms involved in HI-induced tissue damage start immediately after HI and extend for days. Acetylcholine is an important neurotransmitter in the central nervous system and exerts a protector effect on tissue damage by modulating inflammation, and cholinesterase inhibitors have shown neuroprotective properties and their action are often attributed to inhibition of the immune response. The administration of Huperzia quadrifariata alkaloid extract (HqAE), with potent and selective cholinesterase inhibitor properties, will reduce the HI induced behavioral deficits and tissue damage. A total of 84 newborn Wistar rat pups at post natal day 7 (PND7) were subjected to right carotid occlusion followed by 1 h of hypoxia (8% of O2) and i.p. injections of saline, vehicle or HqAE (10 mg/kg). Morris Water Maze and inhibitory avoidance tests were used to assess the cognitive function. Flow cytometry was performed at PND11. Histological analysis was performed at PND45. HqAE treatment was able to prevent the HI induced cognitive deficits in both tests and, at PND45, histological analysis showed that HqAE treatment reduced hippocampus tissue damage. Flow cytometry of the injured hippocampus revealed that the treatment was able to reduce cellular death and the number of infiltrating T cells. Altogether, these results show the therapeutic potential of the Huperzia quadrifariata alkaloid extract to prevent cognitive deficits and histological damage caused by neonatal hypoxia-ischemia, probably by reducing cellular death and T cell mobilization.
authors.affiliation: Post-graduation Program of Neurosciences, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. felipe.odorcyk@gmail.com.
authors.forename: F K
authors.initials: FK
authors.lastname: Odorcyk
authors.affiliation: Post-graduation Program of Neurosciences, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: E F
authors.initials: EF
authors.lastname: Sanches
authors.affiliation: Post-graduation Program of Neurosciences, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: F C
authors.initials: FC
authors.lastname: Nicola
authors.affiliation: Departamento de Bioquímica, Instituto das Ciências da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo 90035-003, Porto Alegre, RS, Brazil.
authors.forename: J
authors.initials: J
authors.lastname: Moraes
authors.affiliation: Departamento de Bioquímica, Instituto das Ciências da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo 90035-003, Porto Alegre, RS, Brazil.
authors.forename: L F
authors.initials: LF
authors.lastname: Pettenuzzo
authors.affiliation: Departamento de Bioquímica, Instituto das Ciências da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo 90035-003, Porto Alegre, RS, Brazil.
authors.forename: J
authors.initials: J
authors.lastname: Kolling
authors.affiliation: Departamento de Bioquímica, Instituto das Ciências da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo 90035-003, Porto Alegre, RS, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Siebert
authors.affiliation: Departamento de Bioquímica, Instituto das Ciências da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo 90035-003, Porto Alegre, RS, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Longoni
authors.affiliation: Department of Pharmaceutical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: E L
authors.initials: EL
authors.lastname: Konrath
authors.affiliation: Departamento de Bioquímica, Instituto das Ciências da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo 90035-003, Porto Alegre, RS, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Wyse
authors.affiliation: Departamento de Bioquímica, Instituto das Ciências da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo 90035-003, Porto Alegre, RS, Brazil.
authors.forename: C A
authors.initials: CA
authors.lastname: Netto
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D002800:Cholinesterase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D032501:Huperzia; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000517:prevention & control; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D010936:Plant Extracts
keywords: Cholinesterase inhibitor; Huperzia quadrifariata; Hypoxia–ischemia; Inflammation; Memory