Separate administration of ammonium pyrrolidinedithiocarbamate and phorbol myristate acetate at early and late stages decreases secondary brain injury following intracerebral haemorrhage in rats via the NF-κB pathway

Administration of both PDTC at the early stage and PMA at the late stage reduced perihematomal cell death after ICH, and using the two reagents together had a stronger anti-apoptotic effect than separate usage.

Rats were divided into a sham group, ICH group, early NF-kB-inhibiting group using ammonium pyrrolidinedithiocarbamate (PDTC; group A, p65 subunit was dominant and inhibited at the early stage), late NF-kB-activating group using phorbol myristate acetate (PMA; group B, c-Rel was dominant and promoted at the late stage), and early NF-kB-inhibiting and late-activating group (group C, p65 subunit was inhibited at the early stage and c-Rel was promoted at the late stage). At preset time points after ICH, perihematomal tissue was obtained for detection of NF-kB activation, cell death, and expression of caspase-3, Bcl-2, and NF-kB subunits, to evaluate of the effect of PDTC and PMA.

Rats were divided into a sham group, ICH group, early NF-kB-inhibiting group using ammonium pyrrolidinedithiocarbamate (PDTC; group A, p65 subunit was dominant and inhibited at the early stage), late NF-kB-activating group using phorbol myristate acetate (PMA; group B, c-Rel was dominant and promoted at the late stage), and early NF-kB-inhibiting and late-activating group (group C, p65 subunit was inhibited at the early stage and c-Rel was promoted at the late stage). At preset time points after ICH, perihematomal tissue was obtained for detection of NF-kB activation, cell death, and expression of caspase-3, Bcl-2, and NF-kB subunits, to evaluate of the effect of PDTC and PMA.

At four days after ICH, p65 expression (p < 0.01) and the number of TUNEL-positive cells (p < 0.01) in group A were significantly lower than in the ICH group. At 10 days after ICH, c-Rel expression in groups B and C was significantly higher than in other groups (p < 0.01 for all). TUNEL-positive cell numbers in groups A and B were significantly lower than in the ICH group, though more numerous than in group C (p < 0.01 for all). Conclusions: Administration of both PDTC at the early stage and PMA at the late stage reduced perihematomal cell death after ICH, and using the two reagents together had a stronger anti-apoptotic effect than separate usage.