Details

Autor(en) / Beteiligte

• Fabres, Rafael Bandeira
• Nunes, Ricardo Ribeiro
• de Medeiros de Mattos, Marcel
• Andrade, Mirella Kielek Galvan
• Martini, Ana Paula Rodrigues
• Tassinari, Isadora D’Ávila
• Sanches, Eduardo Farias
• de Fraga, Luciano Stürmer
• Netto, Carlos Alexandre

Titel

Therapeutic hypothermia for the treatment of neonatal hypoxia-ischemia: sex-dependent modulation of reactive astrogliosis

Ist Teil von

• Metabolic brain disease, 2022-10, Vol.37 (7), p.2315-2329

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2022

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• Therapeutic hypothermia (TH) is the standard treatment for neonatal hypoxia-ischemia (HI) with a time window limited up to 6 h post injury. However, influence of sexual dimorphism in the therapeutic window for TH has not yet been elucidated in animal models of HI. Therefore, the aim of this study was to investigate the most effective time window to start TH in male and female rats submitted to neonatal HI. Wistar rats (P7) were divided into the following groups: NAÏVE and SHAM (control groups), HI (submitted to HI) and TH (submitted to HI and TH; 32ºC for 5 h). TH was started at 2 h (TH-2 h group), 4 h (TH-4 h group), or 6 h (TH-6 h group) after HI. At P14, animals were subjected to behavioural tests, volume of lesion and reactive astrogliosis assessments. Male and female rats from the TH-2 h group showed reduction in the latency of behavioral tests, and decrease in volume of lesion and intensity of GFAP immunofluorescence. TH-2 h females also showed reduction of degenerative cells and morphological changes in astrocytes. Interestingly, females from the TH-6 h group showed an increase in volume of lesion and in number of degenerative hippocampal cells, associated with worse behavioral performance. Together, these results indicate that TH neuroprotection is time- and sex-dependent. Moreover, TH started later (6 h) can worsen volume of brain lesion in females. These data indicate the need to develop specific therapeutic protocols for each sex and reinforce the importance of early onset of the hypothermic treatment.