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Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia.

Blanco-Alvarez VM, Soto-Rodriguez G, Gonzalez-Barrios JA, Martinez-Fong D, Brambila E, Torres-Soto M, Aguilar-Peralta AK, Gonzalez-Vazquez A, Tomás-Sanchez C, Limón ID, Eguibar JR, Ugarte A, Hernandez-Castillo J, Leon-Chavez BA - Neural Plast. (2015)

Bottom Line: Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia.Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat.These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

View Article: PubMed Central - PubMed

Affiliation: Facultad de Ciencias Químicas, BUAP, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.

ABSTRACT
Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

No MeSH data available.


Related in: MedlinePlus

Effect of the subacute administration of zinc on CCR2 immunoreactivity after CCAO. Representative micrographs of CCR2 immunofluorescence ((a) to (o)) using a rabbit antibody against CCR2 and a goat antibody anti-rabbit IgG conjugated with fluorescein isothiocyanate (green color). The cerebral region was identified with propidium iodide (red color) counterstaining. Graphs ((p), (q), (r), (s), and (t)) show the normalized values of CCR2-IR with respect to control IR for CCAO (Figures 3(a)to 3(o)) and subacute administration of zinc ((a) to (o)). The IR was measured using ImageJ 1.45 of the National Institute of Health. CA, Cornu Ammonis, and DG, dentate gyrus, of the hippocampus. LV, layer V of the cerebral cortex. Plexus, choroid plexus. Values are expressed as the mean ± SEM from 3 rats for each experimental condition. ∗, significant when compared with the control group; ANOVA test and post hoc Dunnett's test. †, significant when compared between groups; unpaired Student's t-test. P < 0.05.
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fig4: Effect of the subacute administration of zinc on CCR2 immunoreactivity after CCAO. Representative micrographs of CCR2 immunofluorescence ((a) to (o)) using a rabbit antibody against CCR2 and a goat antibody anti-rabbit IgG conjugated with fluorescein isothiocyanate (green color). The cerebral region was identified with propidium iodide (red color) counterstaining. Graphs ((p), (q), (r), (s), and (t)) show the normalized values of CCR2-IR with respect to control IR for CCAO (Figures 3(a)to 3(o)) and subacute administration of zinc ((a) to (o)). The IR was measured using ImageJ 1.45 of the National Institute of Health. CA, Cornu Ammonis, and DG, dentate gyrus, of the hippocampus. LV, layer V of the cerebral cortex. Plexus, choroid plexus. Values are expressed as the mean ± SEM from 3 rats for each experimental condition. ∗, significant when compared with the control group; ANOVA test and post hoc Dunnett's test. †, significant when compared between groups; unpaired Student's t-test. P < 0.05.

Mentions: The regional localization of CCR2 was explored using indirect immunofluorescence and propidium iodide counterstaining. CCR2 immunoreactivity (IR) was mainly localized in the granular zone of hippocampus (Figures 3 and 4) and in the pyramidal cells of layer III (data not shown) and V of cerebral cortex (Figures 3 and 4). The net intensity of CCR2 immunofluorescence was plotted (number of pixels per area) comparing each region with CCAO of Figures 3(a)–3(o) against subacute administration of zinc after CCAO in Figures 4(a)–4(o), and these are showed in the graphs of Figure 4 ((p), (q), (r), (s), and (t)). In the CA1 region, CCAO (Figure 3(c)) caused a significant decrease in CCR2-IR by 79 ± 15% at 168 h after reperfusion (Figure 4(p)). In the cerebral cortex (Figure 3(k)), the decrease was 46 ± 2% at 24 h after reperfusion (Figure 4(s)) and in choroid plexus (Figure 3(o)); CCAO caused a decrease of CCR2-IR by 31 ± 0.5% at 168 h after reperfusion (Figure 4(t)). CCAO caused the loss of granular cell cytoarchitecture of CA1, CA3, and DG regions (Figures 3(a)–3(i)). Whereas the subacute administration of zinc caused a significant increase of CCR2 IR in the CA1 after CCAO at 24 h (Figure 4(b)) by 202 ± 5% and at 168 h after reperfusion (Figure 4(c)) by 248 ± 3% as shown in the graph (Figure 4(p)). The net intensity in CA3 after CCAO at 24 h (Figure 4(e)) increased 44 ± 2% and at 168 h after reperfusion (Figure 4(f)) by 62 ± 2% as shown in the graph (Figure 4(q)). In the DG (Figures 4(h) and 4(i)), CCR2 IR increased by 53 ± 3% at 24 h and by 75 ± 2% at 168 h after reperfusion (Figure 4(r)). In layer V of cerebral cortex (Figures 4(k) and 4(l)), CCR2 IR increased by 337 ± 5% at 24 h and by 324 ± 7% at 168 h after reperfusion (Figure 4(s)). In the choroid plexus (Figure 4(o)), CCR2 IR increased by 88 ± 2% at 168 h after reperfusion (Figure 4(t)). In choroid plexus, the CCR2 IR increased at 168 h after reperfusion (Figure 4(o)) by 88 ± 2% as shown in the graph (Figure 4(t)).


Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia.

Blanco-Alvarez VM, Soto-Rodriguez G, Gonzalez-Barrios JA, Martinez-Fong D, Brambila E, Torres-Soto M, Aguilar-Peralta AK, Gonzalez-Vazquez A, Tomás-Sanchez C, Limón ID, Eguibar JR, Ugarte A, Hernandez-Castillo J, Leon-Chavez BA - Neural Plast. (2015)

Effect of the subacute administration of zinc on CCR2 immunoreactivity after CCAO. Representative micrographs of CCR2 immunofluorescence ((a) to (o)) using a rabbit antibody against CCR2 and a goat antibody anti-rabbit IgG conjugated with fluorescein isothiocyanate (green color). The cerebral region was identified with propidium iodide (red color) counterstaining. Graphs ((p), (q), (r), (s), and (t)) show the normalized values of CCR2-IR with respect to control IR for CCAO (Figures 3(a)to 3(o)) and subacute administration of zinc ((a) to (o)). The IR was measured using ImageJ 1.45 of the National Institute of Health. CA, Cornu Ammonis, and DG, dentate gyrus, of the hippocampus. LV, layer V of the cerebral cortex. Plexus, choroid plexus. Values are expressed as the mean ± SEM from 3 rats for each experimental condition. ∗, significant when compared with the control group; ANOVA test and post hoc Dunnett's test. †, significant when compared between groups; unpaired Student's t-test. P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4556331&req=5

fig4: Effect of the subacute administration of zinc on CCR2 immunoreactivity after CCAO. Representative micrographs of CCR2 immunofluorescence ((a) to (o)) using a rabbit antibody against CCR2 and a goat antibody anti-rabbit IgG conjugated with fluorescein isothiocyanate (green color). The cerebral region was identified with propidium iodide (red color) counterstaining. Graphs ((p), (q), (r), (s), and (t)) show the normalized values of CCR2-IR with respect to control IR for CCAO (Figures 3(a)to 3(o)) and subacute administration of zinc ((a) to (o)). The IR was measured using ImageJ 1.45 of the National Institute of Health. CA, Cornu Ammonis, and DG, dentate gyrus, of the hippocampus. LV, layer V of the cerebral cortex. Plexus, choroid plexus. Values are expressed as the mean ± SEM from 3 rats for each experimental condition. ∗, significant when compared with the control group; ANOVA test and post hoc Dunnett's test. †, significant when compared between groups; unpaired Student's t-test. P < 0.05.
Mentions: The regional localization of CCR2 was explored using indirect immunofluorescence and propidium iodide counterstaining. CCR2 immunoreactivity (IR) was mainly localized in the granular zone of hippocampus (Figures 3 and 4) and in the pyramidal cells of layer III (data not shown) and V of cerebral cortex (Figures 3 and 4). The net intensity of CCR2 immunofluorescence was plotted (number of pixels per area) comparing each region with CCAO of Figures 3(a)–3(o) against subacute administration of zinc after CCAO in Figures 4(a)–4(o), and these are showed in the graphs of Figure 4 ((p), (q), (r), (s), and (t)). In the CA1 region, CCAO (Figure 3(c)) caused a significant decrease in CCR2-IR by 79 ± 15% at 168 h after reperfusion (Figure 4(p)). In the cerebral cortex (Figure 3(k)), the decrease was 46 ± 2% at 24 h after reperfusion (Figure 4(s)) and in choroid plexus (Figure 3(o)); CCAO caused a decrease of CCR2-IR by 31 ± 0.5% at 168 h after reperfusion (Figure 4(t)). CCAO caused the loss of granular cell cytoarchitecture of CA1, CA3, and DG regions (Figures 3(a)–3(i)). Whereas the subacute administration of zinc caused a significant increase of CCR2 IR in the CA1 after CCAO at 24 h (Figure 4(b)) by 202 ± 5% and at 168 h after reperfusion (Figure 4(c)) by 248 ± 3% as shown in the graph (Figure 4(p)). The net intensity in CA3 after CCAO at 24 h (Figure 4(e)) increased 44 ± 2% and at 168 h after reperfusion (Figure 4(f)) by 62 ± 2% as shown in the graph (Figure 4(q)). In the DG (Figures 4(h) and 4(i)), CCR2 IR increased by 53 ± 3% at 24 h and by 75 ± 2% at 168 h after reperfusion (Figure 4(r)). In layer V of cerebral cortex (Figures 4(k) and 4(l)), CCR2 IR increased by 337 ± 5% at 24 h and by 324 ± 7% at 168 h after reperfusion (Figure 4(s)). In the choroid plexus (Figure 4(o)), CCR2 IR increased by 88 ± 2% at 168 h after reperfusion (Figure 4(t)). In choroid plexus, the CCR2 IR increased at 168 h after reperfusion (Figure 4(o)) by 88 ± 2% as shown in the graph (Figure 4(t)).

Bottom Line: Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia.Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat.These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

View Article: PubMed Central - PubMed

Affiliation: Facultad de Ciencias Químicas, BUAP, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.

ABSTRACT
Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

No MeSH data available.


Related in: MedlinePlus