Neuroprotective effect of nanoparticle-bounded brain derived neurotrophic factor (BDNF) in rats with experimental haemorrhagic stroke / Sayyidah Maryamul Azra Zul Ramli

Brain-derived neurotrophic factor (BDNF) plays an essential role in brain plasticity and
repair. At the same time, nanoparticle (NPs) poly (lactic-co-glycolic acid) (PLGA) has
been proven either in-vivo or in-vitro as potential carriers for drugs across the BBB,
with advantages of enhanced drug efficiency and safety. This study was aimed to
investigate the neuroprotective effect of BDNF-PLGA nanoparticles on experimental
haemorrhagic stroke (HS) in rats. Sprague-Dawley rats were divided into 6 groups;
group 1, sham operation while group 2 to 6 were induced with HS. 15 minutes after
induced, all groups were treated with respective formulations intravenously: groups 1
and 2 were treated with saline; group 3 was treated with empty PLGA NPs; group 4
with PLGA NPs coated with surfactant; group 5 with BDNF-loaded PLGA NPs and
group 6 with BDNF-loaded PLGA NPs coated with surfactant. Behavioural
assessments were performed after treatment on days 1, 3 and 7. On day 7, rats were
sacrificed, and brain was taken for histological and immunohistochemical analysis.
Caspase-3 staining showed that treatment with BDNF-loaded PLGA NPs exhibited
significant lower in apoptosis compared with other HS groups. Groups 2, 3 and 4
demonstrated a significant increase in glial cells when compared to BDNF treated
groups. Rats treated with BDNF-loaded PLGA NPs also exhibited low expression of
synaptophysin. Open field test showed that treatment with BDNF-loaded PLGA NPs
produced high score in rearing and total distance travelled indicating improvement in
locomotor activity. BDNF NPs treated group showed improved rotarod performance
indicating improvement in their motor learning and coordination. Rats treated with
BDNF-loaded PLGA NPs also exhibited increased grip strength as evidence of motor
neuroprotection. Hence, BDNF-loaded PLGA NPs may have neuroprotective effect on
experimental HS in rats.