{"doi":"10.1002/nep3.70003","title":"Protecting the brain from multifaceted damage and promoting recovery","abstract":"Controlling and mitigating the burden and impact of neurodegenerative diseases has three major components. The first is prevention, for instance, aiming at risk factors and comorbidities that increase the incidence of acute or chronic neurodegenerative diseases. This requires a detailed understanding of the prevalence of these factors as well as their pathomechanistical impact on neurodegenerative diseases, plus of efficient ways to control them. It also requires knowledge about potential protective factors. The second component is active medical treatment of a manifesting neurodegenerative conditions by either targeting its cause or at least its most disabling symptoms. This component is addressed by most therapeutic research activities. The third component focuses on long-term outcome. It requires a better mechanistic understanding of neurodegeneration sequelae as well as of the brain's unique capacity to respond to pathological challenges, for instance, by synaptic and circuit plasticity. Whereas previous issues of Neuroprotection often focused on the second component, the recent one will put more emphasis on the first and third component. It will deal with both central nervous system (CNS) disorders caused by acute neurodegeneration, such as ischemic stroke, as well as less acute diseases, including Alzheimer's (AD) and Parkinson's disease (PD). Advances in acute stroke management have led to increased survival and better functional outcome. On the other hand, increased stroke survival, as well as a combination of higher life expectancy and rising stroke incidence in middle-aged patients, have also increased the prevalence of long-term complications of ischemic stroke, such as post-stroke cognitive impairment (PSCI) and post-stroke dementia (PSD). Secondary neurodegeneration (SND) after stroke has been connected to both PSCI and PSD. A loss of functional input from brain regions affected by the stroke is considered a main cause of SND but SND is also observed in areas not directly connected to the affected regions. Thus, the mechanisms underlying SND are presumably more complex and not yet fully understood. The review paper by Stuckey and colleagues provides a superb overview of our current understanding of SND. The authors focus on brain regions often affected by SND, that is, the prefrontal cortex, thalamus, basal ganglia, amygdala, and the hippocampus, and describe the functional, anatomical, and molecular changes observed in these regions. This provides a detailed picture of SND and the underlying pathomechanisms which also fosters a better understanding of PSCI and PSD in the context of SND. Importantly, the review points at multiple potential therapeutic targets that could be addressed by secondary cerebroprotective strategies to be applied in subacute and chronic stroke stages. This has the potential to contribute to more holistic treatment strategies, further improving overall stroke outcome and supporting the beneficial impact of recanalization therapies.1 The complex etiology of ischemic stroke is well known. Numerous reports clearly show that highly prevalent comorbidities such as hypertension, dyslipidemia, hyperglycemia, hyperuricemia, and atrial fibrillation are substantial risk factors of ischemic stroke. Moreover, the presence of these comorbidities can alter and aggravate stroke impact.2 Thus, a detailed understanding of stroke comorbidities and their prevalence is essential for stroke management. The review by Datta et al. describes the role and impact of important comorbidities on stroke, also summarizing research findings describing comorbidity-related pathomechanisms. However, the review goes beyond that by presenting comprehensive data on the incidence and prevalence of stroke risk factors in Southeast Asian countries. The reason for this is that high stroke incidence, as well as high stroke-related mortality, are reported in these countries, whereas available demographic information on comorbidities ","journal":"Neuroprotection/Neuroprotection (Chichester, England. Print)","year":2025,"id":520844,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":320471,"name":"Xunming Ji","orcid":"0000-0003-0293-2744","position":1,"is_corresponding":false},{"id":746253,"name":"Shen Li","orcid":"0000-0001-6779-9812","position":2,"is_corresponding":false},{"id":851068,"name":"Johannes Boltze","orcid":"0000-0003-3956-4164","position":3,"is_corresponding":false},{"id":416236,"name":"Piotr Walczak","orcid":"0000-0002-3733-3322","position":0,"is_corresponding":true}],"reference_count":7,"raw_metadata":null,"created_at":"2026-07-19T02:49:32.958846Z","pmid":"40276372","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}