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The role of microclot formation in an acute subarachnoid hemorrhage model in the rabbit.

Andereggen L, Neuschmelting V, von Gunten M, Widmer HR, Fandino J, Marbacher S - Biomed Res Int (2014)

Bottom Line: Our results showed significantly more TUNEL-positive cells (SAH: 115 ± 13; controls: 58 ± 10; P = 0.016) and fibrinogen-positive microthromboemboli (SAH: 9 ± 2; controls: 2 ± 1; P = 0.03) in the hippocampus after aneurysmal SAH.We found clear evidence of early microclot formation in a rabbit model of acute SAH.The extent of microthrombosis did not correlate with early apoptosis or CPP depletion after SAH; however, the total number of TUNEL positive cells in the cortex and the hippocampus significantly correlated with mean CPP reduction during the phase of maximum depletion after SAH induction.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Bern University Hospital, Inselspital Bern, 3012 Bern, Switzerland ; Laboratories for Neuroscience Research in Neurosurgery, Boston Children's Hospital, Boston, MA 02115, USA ; Harvard Medical School, Boston, MA 02115, USA.

ABSTRACT

Background: Microvascular dysfunction and microthrombi formation are believed to contribute to development of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH).

Objective: This study aimed to determine (i) extent of microthrombus formation and neuronal apoptosis in the brain parenchyma using a blood shunt SAH model in rabbits; (ii) correlation of structural changes in microvessels with EBI characteristics.

Methods: Acute SAH was induced using a rabbit shunt cisterna magna model. Extent of microthrombosis was detected 24 h post-SAH (n = 8) by fibrinogen immunostaining, compared to controls (n = 4). We assessed apoptosis by terminal deoxynucleotidyl transferase nick end labeling (TUNEL) in cortex and hippocampus.

Results: Our results showed significantly more TUNEL-positive cells (SAH: 115 ± 13; controls: 58 ± 10; P = 0.016) and fibrinogen-positive microthromboemboli (SAH: 9 ± 2; controls: 2 ± 1; P = 0.03) in the hippocampus after aneurysmal SAH.

Conclusions: We found clear evidence of early microclot formation in a rabbit model of acute SAH. The extent of microthrombosis did not correlate with early apoptosis or CPP depletion after SAH; however, the total number of TUNEL positive cells in the cortex and the hippocampus significantly correlated with mean CPP reduction during the phase of maximum depletion after SAH induction. Both microthrombosis and neuronal apoptosis may contribute to EBI and subsequent DCI.

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In the SAH group, a significant reduction in CPP was observed within the first three minutes of the phase of maximum depletion compared to the baseline or the steady state (P < 0.001). A significant positive linear correlation between the mean CPP during the phase of maximum depletion after induced SAH and the total number of TUNEL positive cells was found in both the cortex (r2 = 0.53, P = 0.007; (a)) and the hippocampus (r2 = 0.60, P = 0.003; (b)). There was no correlation between CPP depletion and fibrinogen positive microvessels in either cortex (r2 = 0.17, (c)) or hippocampus (r2 = 0.22, (d)). Graphs include the 95% confidence intervals.
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fig4: In the SAH group, a significant reduction in CPP was observed within the first three minutes of the phase of maximum depletion compared to the baseline or the steady state (P < 0.001). A significant positive linear correlation between the mean CPP during the phase of maximum depletion after induced SAH and the total number of TUNEL positive cells was found in both the cortex (r2 = 0.53, P = 0.007; (a)) and the hippocampus (r2 = 0.60, P = 0.003; (b)). There was no correlation between CPP depletion and fibrinogen positive microvessels in either cortex (r2 = 0.17, (c)) or hippocampus (r2 = 0.22, (d)). Graphs include the 95% confidence intervals.

Mentions: CPP showed maximal depletion within the first 3 minutes after induction of SAH (Figure 3(e)). A significant linear correlation was observed between CPP reduction within the first three minutes after SAH and the total number of TUNEL positive cells in the cortex (reg coeff r = 0.73, r2 = 0.53, P = 0.007; Figure 4(a)) as well as in the hippocampus (reg coeff r = 0.77, r2 = 0.60, P = 0.003; Figure 4(b)). However, no significant correlation was detected between relative CPP depletion within the first three minutes and the number of fibrinogen stained microvessels in the cortex (reg coeff r = 0.42, r2 = 0.17, P = 0.18; Figure 4(c)) or in the hippocampus (reg coeff r = 0.47, r2 = 0.22, P = 0.12; Figure 4(d)).


The role of microclot formation in an acute subarachnoid hemorrhage model in the rabbit.

Andereggen L, Neuschmelting V, von Gunten M, Widmer HR, Fandino J, Marbacher S - Biomed Res Int (2014)

In the SAH group, a significant reduction in CPP was observed within the first three minutes of the phase of maximum depletion compared to the baseline or the steady state (P < 0.001). A significant positive linear correlation between the mean CPP during the phase of maximum depletion after induced SAH and the total number of TUNEL positive cells was found in both the cortex (r2 = 0.53, P = 0.007; (a)) and the hippocampus (r2 = 0.60, P = 0.003; (b)). There was no correlation between CPP depletion and fibrinogen positive microvessels in either cortex (r2 = 0.17, (c)) or hippocampus (r2 = 0.22, (d)). Graphs include the 95% confidence intervals.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109416&req=5

fig4: In the SAH group, a significant reduction in CPP was observed within the first three minutes of the phase of maximum depletion compared to the baseline or the steady state (P < 0.001). A significant positive linear correlation between the mean CPP during the phase of maximum depletion after induced SAH and the total number of TUNEL positive cells was found in both the cortex (r2 = 0.53, P = 0.007; (a)) and the hippocampus (r2 = 0.60, P = 0.003; (b)). There was no correlation between CPP depletion and fibrinogen positive microvessels in either cortex (r2 = 0.17, (c)) or hippocampus (r2 = 0.22, (d)). Graphs include the 95% confidence intervals.
Mentions: CPP showed maximal depletion within the first 3 minutes after induction of SAH (Figure 3(e)). A significant linear correlation was observed between CPP reduction within the first three minutes after SAH and the total number of TUNEL positive cells in the cortex (reg coeff r = 0.73, r2 = 0.53, P = 0.007; Figure 4(a)) as well as in the hippocampus (reg coeff r = 0.77, r2 = 0.60, P = 0.003; Figure 4(b)). However, no significant correlation was detected between relative CPP depletion within the first three minutes and the number of fibrinogen stained microvessels in the cortex (reg coeff r = 0.42, r2 = 0.17, P = 0.18; Figure 4(c)) or in the hippocampus (reg coeff r = 0.47, r2 = 0.22, P = 0.12; Figure 4(d)).

Bottom Line: Our results showed significantly more TUNEL-positive cells (SAH: 115 ± 13; controls: 58 ± 10; P = 0.016) and fibrinogen-positive microthromboemboli (SAH: 9 ± 2; controls: 2 ± 1; P = 0.03) in the hippocampus after aneurysmal SAH.We found clear evidence of early microclot formation in a rabbit model of acute SAH.The extent of microthrombosis did not correlate with early apoptosis or CPP depletion after SAH; however, the total number of TUNEL positive cells in the cortex and the hippocampus significantly correlated with mean CPP reduction during the phase of maximum depletion after SAH induction.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Bern University Hospital, Inselspital Bern, 3012 Bern, Switzerland ; Laboratories for Neuroscience Research in Neurosurgery, Boston Children's Hospital, Boston, MA 02115, USA ; Harvard Medical School, Boston, MA 02115, USA.

ABSTRACT

Background: Microvascular dysfunction and microthrombi formation are believed to contribute to development of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH).

Objective: This study aimed to determine (i) extent of microthrombus formation and neuronal apoptosis in the brain parenchyma using a blood shunt SAH model in rabbits; (ii) correlation of structural changes in microvessels with EBI characteristics.

Methods: Acute SAH was induced using a rabbit shunt cisterna magna model. Extent of microthrombosis was detected 24 h post-SAH (n = 8) by fibrinogen immunostaining, compared to controls (n = 4). We assessed apoptosis by terminal deoxynucleotidyl transferase nick end labeling (TUNEL) in cortex and hippocampus.

Results: Our results showed significantly more TUNEL-positive cells (SAH: 115 ± 13; controls: 58 ± 10; P = 0.016) and fibrinogen-positive microthromboemboli (SAH: 9 ± 2; controls: 2 ± 1; P = 0.03) in the hippocampus after aneurysmal SAH.

Conclusions: We found clear evidence of early microclot formation in a rabbit model of acute SAH. The extent of microthrombosis did not correlate with early apoptosis or CPP depletion after SAH; however, the total number of TUNEL positive cells in the cortex and the hippocampus significantly correlated with mean CPP reduction during the phase of maximum depletion after SAH induction. Both microthrombosis and neuronal apoptosis may contribute to EBI and subsequent DCI.

Show MeSH
Related in: MedlinePlus