Brain-derived neurotrophic factor delivered to the brain using poly (lactide-co-glycolide) nanoparticles improves neurological and cognitive outcome in mice with traumatic brain injury

Figures & data

Table 1. Neurological severity score test.

No	Task	Score
1	Exit circle within 3 min	1
2	Seeking behavior	1
3	Startle reflex	1
4	Straight walk	1
5	Mono- or hemiparesis	1
6	Balance on 0.7-cm-wide beam during 10 s	1
7	3-cm-wide beam walk within 3 min	1
8	2-cm-wide beam walk within 3 min	1
9	1-cm-wide beam walk within 3 min	1
10	Balance on 0.5-cm-diameter round stick during 10 s	1

Figure 1. BDNF concentration. The efficiency of BDNF adsorption on nanoparticles was measured after particle separation by filtration through a membrane filter (220 nm). Initial concentration was 25 μg/ml.

Figure 2. A bar graphs depicting brain-derived neurotrophic factor (BDNF) concentrations (pg/mg protein) measured by enzyme-linked immunosorbent assay (ELISA) in the brain of male C57Bl/6 mice at one hour post-injection of phosphate-buffered saline (PBS); solution of recombinant BDNF in PBS (PBS + BDNF); solution of recombinant BDNF in PBS with poloxamer 188 (PBS + BDNF + PX); suspension of poly(lactic-co-glycolic acid) nanoparticles (NP) with adsorbed BDNF on their surface (PBS + NP + BDNF); suspension of NP with adsorbed BDNF on their surface and coated by poloxamer 188 (PBS + NP + BDNF + PX). Sham: left brain hemisphere of sham-operated animals; Ipsi: ipsilateral brain hemisphere of animals with traumatic brain injury (TBI); Contra: contralateral brain hemisphere of animals with TBI. Values are mean ± SD, n = 6; *p < 0.05, **p < 0.01 and ***p < 0.001 versus PBS group; #p < 0.05, ##p < 0.01 and ###p < 0.001 versus PBS + NP + BDNF + PX group. Repeated measures two-way ANOVA with Bonferroni post-hoc analysis. ^p < 0.05, ^^p < 0.01 and ^^^p < 0.001 versus Sham group. Repeated measures one-way ANOVA with Bonferroni post-hoc analysis.

Figure 3. A bar graphs depicting neurological severity score (NSS) in male C57Bl/6 mice with brain trauma at 1 h, 4 h, 1d, 2d, 3d and 7d post-injury. 3 h post-injury, intravenous injection in volume 0.2 ml was administered with the following solutions: phosphate-buffered saline (PBS); solution of recombinant BDNF in PBS (PBS + BDNF); solution of recombinant BDNF in PBS with poloxamer 188 (PBS + BDNF + PX); suspension of empty poly(lactic-co-glycolic acid) nanoparticles (NP); suspension of NP with adsorbed BDNF on their surface (PBS + NP + BDNF); suspension of NP with adsorbed BDNF on their surface and coated by poloxamer 188 (PBS + NP + BDNF + PX). Values are mean ± SD, n = 6; *p < 0.05, **p < 0.01 and ***p < 0.001 versus PBS + NP + BDNF + PX group. Repeated measures two-way ANOVA with Bonferroni post-hoc analysis.

Figure 4. Mean latent time (sec ± m, n = 6) that the mice spent at the light chamber, at day 7 after the brain injury (cutoff time 180 s). Group Sham includes mice with sham operation. The rest groups include mice subjected to TBI and received IV injection 3 h post-injury of following solutions: PBS: control group with PBS solution as drug vehicle; PBS + BNDF: solution of BDNF (5 μg/per mouse); PBS + BNDF + PX: 1% solution of Poloxamer®188 with BDNF (5 μg/per mouse); PBS + NP: solution of empty 2% PLGA NPs; PBS + NP + BNDF: solution of BDNF (5 μg/per mouse) adsorbed on PLGA NP; PBS + NP + BDNF + PX: solution of BDNF (5 μg/per mouse) adsorbed on PLGA NP coated with Poloxamer®188. *p < 0.05, **p < 0.01, ***p < 0.001 versus PBS + NP + BDNF + PX group; #p < 0.05, ##p < 0.01, ###p < 0.001 versus control (PBS) group repeated measures one-way ANOVA, with Bonferroni’s multiple comparison tests.