Delayed CTP-Derived Deep Venous Outflow: A Novel Predictor of Striatocapsular Infarction after M1 Thrombectomy.

BACKGROUND AND PURPOSE: Isolated striatocapsular infarction occurs commonly in patients with ischemic stroke following M1 thrombectomy. We aimed to explore the correlation between CTP-derived parameters of deep venous outflow at presentation and subsequent striatocapsular infarction in a retrospective cohort of such patients. MATERIALS AND METHODS: TTP and peak enhancement were measured on CTP-derived time-attenuation curves of the internal cerebral and thalamostriate veins bilaterally. The difference in TTP (ΔTTP) and the relative decrease in venous enhancement between the ischemic and normal sides were calculated. NCCT performed 24 (SD, 12) hours postthrombectomy was used to determine tissue fate in the caudate head, caudate body, lentiform nucleus, and internal capsule. Striatocapsular ischemia (striatocapsular infarction-positive) was defined as infarction and striatocapsular injury as either infarction, contrast enhancement, or hemorrhagic transformation in ≥1 of these regions. A striatocapsular ischemia score was calculated (0 = no ischemic region, 1 = 1 ischemic region, 2 = ≥2 ischemic regions). RESULTS: One hundred sixteen patients were included in the analysis. Sixty-one patients had striatocapsular infarction (striatocapsular infarction-positive). The mean thalamostriate ΔTTP was 1.95 (SD, 1.9) seconds for patients positive for striatocapsular infarction and 0.79 (SD, 2.1) for patients negative for it (P = .010). Results were similar for striatocapsular injury. The mean thalamostriate ΔTTP was 0.79 (SD, 2.1), 1.68 (SD, 1.4), and 2.05 (SD, 2) for striatocapsular infarction scores of 0, 1, and 2, respectively (P = .030). CONCLUSIONS: CTP-derived thalamostriate ΔTTP is an excellent surrogate marker for striatocapsular infarction in patients post-M1 thrombectomy. The novel approach of extracting venous outflow parameters from CTP has numerous potential applications and should be further explored.

PARP-1 is required for retrieval of cocaine-associated memory by binding to the promoter of a novel gene encoding a putative transposase inhibitor.

Reward-related memory is an important factor in cocaine seeking. One necessary signaling mechanism for long-term memory formation is the activation of poly(ADP-ribose) polymerase-1 (PARP-1), via poly(ADP-ribosyl)ation. We demonstrate herein that auto-poly(ADP-ribosyl)ation of activated PARP-1 was significantly pronounced during retrieval of cocaine-associated contextual memory, in the central amygdala (CeA) of rats expressing cocaine-conditioned place preference (CPP). Intra-CeA pharmacological and short hairpin RNA depletion of PARP-1 activity during cocaine-associated memory retrieval abolished CPP. In contrast, PARP-1 inhibition after memory retrieval did not affect CPP reconsolidation process and subsequent retrievals. Chromatin immunoprecipitation sequencing revealed that PARP-1 binding in the CeA is highly enriched in genes involved in neuronal signaling. We identified among PARP targets in CeA a single gene, yet uncharacterized and encoding a putative transposase inhibitor, at which PARP-1 enrichment markedly increases during cocaine-associated memory retrieval and positively correlates with CPP. Our findings have important implications for understanding drug-related behaviors, and suggest possible future therapeutic targets for drug abuse.