Decoding spontaneous intracerebral hemorrhage: mechanistic breakthroughs and disruptive revolution in pharmacological treatment.

Spontaneous intracerebral hemorrhage (ICH), especially hypertensive basal ganglia hemorrhage, is a severe, often fatal stroke subtype with high morbidity and mortality. This historical review traces therapeutic progress from the 1960s to the present, emphasizing rehabilitation, peripheral-central nervous system interactions, and clinical outcomes. Molecular mechanisms, early treatments, and advances in interventions are examined. Rehabilitation strategies, such as exercise programs, stem cell therapies, and novel physical modalities, are evaluated for their effects on neuroprotection, neuroplasticity, and functional recovery. Pharmacological approaches during subacute and chronic phases are also reviewed. Clinical trials (phases I-III) are critically assessed for end points and efficacy of combined therapies. This Review highlights emerging paradigms targeting peripheral-central pathways, personalized rehabilitation, and future directions, while addressing research limitations and clinical challenges. Evolution of treatment strategies for intracerebral hemorrhage (ICH). a, Development of treatment drugs for intracerebral hemorrhage. Since the 1990s, pharmacological interventions have evolved, including thrombolytics, anticoagulants, cell-protective drugs, ferroptosis inhibitors, natural medicines, and hydrogen therapy, all aimed at improving patient outcomes. b, Advancements in drug treatments for ICH. Recent therapeutic innovations focus on reducing ICH-related damage, including the use of tranexamic acid for hemorrhage control, ferroptosis inhibitors for preventing delayed cerebral ischemia, and hydrogen therapy to mitigate inflammatory and oxidative stress responses. c, Application of rehabilitation therapy in ICH. Rehabilitation strategies, including physical therapy and pharmacological support, promote functional recovery by enhancing limb function, balance, and coordination while reducing inflammatory responses and accelerating neuroplasticity. d, Traditional treatment methods for ICH. Various traditional Chinese medicine approaches, such as Salvia miltiorrhiza-based adjuvant therapy, acupuncture for blood circulation enhancement, Tuina therapy, and hypothermia treatment, contribute to reducing cell apoptosis and brain edema. e, Current status of clinical trials. Ongoing trials assess drug safety, efficacy, and application across different patient populations, whereas challenges such as patient variability, drug dosage optimization, and administration timing remain crucial for translating research into clinical practice. f, Future prospects. The integration of multidimensional treatment approaches, encompassing gene therapy, exosome therapy, nanotechnology-based drug delivery, hydrogen therapy, and the combination of modern pharmacology with traditional medicine, holds significant promise for refining rehabilitation protocols and enhancing patient outcomes.