Spontaneous intracerebral hemorrhage (SICH) is an acute cerebrovascular event characterized by high mortality and disability rates, accounting for 15–20% of all strokes (1). In elderly populations, factors such as increased vascular fragility, hypertension, and cerebral amyloid angiopathy substantially elevate the risk of SICH, and outcomes in this group are poorer than in younger patients (2). Despite advances in neurosurgical techniques and perioperative management in recent years, clinical treatment of SICH remains highly challenging. In particular, effective hematoma evacuation, mitigation of secondary brain injury, and promotion of neurological recovery remain critical issues in need of resolution.

Current management strategies for SICH include conservative treatment and surgical intervention. Conservative measures focus on blood pressure control, reduction of intracranial pressure, and maintenance of vital signs; however, their efficacy is limited in patients with moderate-to-large hemorrhages or impending herniation (3). Surgical options encompass conventional craniotomy for hematoma removal, minimally invasive puncture and drainage, and microsurgical techniques. Among these, microsurgery, by virtue of its precision and minimally invasive approach, allows for maximal preservation of normal brain tissue while achieving thorough hematoma evacuation, and has become an important treatment modality for SICH recently (4). Patients with cerebellar intracerebral hemorrhage (ICH) were excluded from this study because clot evacuation is rarely performed during decompressive surgery in this population. Although cerebellar and cerebral ICH share many underlying pathophysiological mechanisms—including neurotransmitter alterations contributing to secondary injury—the current evidence regarding neurotransmitter dynamics in cerebellar ICH is limited, and thus focusing on cerebral ICH enhances the consistency of intervention and outcome evaluation. Nevertheless, in elderly patients who often present with multiple comorbidities and reduced physiological reserve, the selection of surgical indications and the prospects for postoperative neurological recovery remain controversial.

Neurotransmitters are key mediators of inter-neuronal communication, and their dynamic balance is essential for normal brain function. It has been shown that, following SICH, hematoma-induced compression and ischemia-hypoxia provoke the excessive release of excitatory neurotransmitters, leading to excitotoxic neuronal injury (5). Concurrent reductions in inhibitory neurotransmitters further exacerbate neurological dysfunction (6). Accordingly, monitoring serum neurotransmitter fluctuations may offer novel biomarkers for assessing the extent of brain injury and predicting prognosis.

To date, few studies have examined the impact of microsurgical intervention on neurotransmitter dynamics in SICH patients, particularly within the elderly cohort. It remains to be determined whether surgical evacuation can effectively suppress the release of excitatory neurotransmitters, restore inhibitory neurotransmitter balance, and thereby improve neurological outcomes. Compared with conventional craniotomy, microsurgery offers the advantages of smaller incisions, clearer operative fields, and more complete hematoma removal, making it especially suitable for deep-seated hemorrhages (e.g., basal ganglia and thalamus) or those located in eloquent brain regions (7). Several clinical investigations have demonstrated that microsurgical techniques can significantly reduce mortality and enhance postoperative neurological scores in SICH patients (8). However, due to diminished cerebral compensatory capacity, elderly patients often exhibit slower postoperative recovery and greater variability in long-term outcomes. Against this backdrop, the present study aims to assess the impact of microsurgical hematoma evacuation on short-term serum neurotransmitter levels in elderly SICH patients and to explore their association with patient prognosis.

The pathophysiological process of SICH is divided into primary and secondary injury phases. Primary injury is induced predominantly by the mass effect of the hematoma, resulting in compression of adjacent brain tissue, increased intracranial pressure, and reduced cerebral perfusion (11). Secondary injury involves complex molecular mechanisms, including inflammatory responses, oxidative stress, blood–brain barrier disruption, and excitotoxicity mediated by excitatory amino acids such as Glu (12). Together, these factors precipitate neuronal apoptosis and neurological deficits, severely compromising patient quality of life and long-term prognosis. With the aging of China’s population, the incidence of SICH in the elderly has risen, imposing a substantial burden on both society and families. Existing studies have demonstrated that direct hematoma mass effect, secondary edema, and inflammatory cascades are the principal drivers of post-hemorrhagic neurological injury (13). Alterations in neurotransmitter levels, particularly Glu and GABA, have been shown to correlate closely with the extent of tissue injury and functional recovery, suggesting their potential utility as early biological markers. Conservative management affords some benefit in blood-pressure control, intracranial pressure reduction, and vital-sign support but provides limited efficacy in hematoma evacuation. In recent years, microsurgical hematoma evacuation has been increasingly adopted for SICH treatment owing to its minimal invasiveness, precise technique, and capacity for thorough clot removal with reduced collateral tissue damage. This approach has been particularly advocated for patients presenting with moderate-to-large hematomas or impending herniation. Nonetheless, the effects of microsurgery on short-term serum neurotransmitter dynamics and long-term neurological recovery in elderly SICH patients remain inadequately characterized.

In the present study of 106 elderly SICH patients undergoing microsurgical evacuation, significant postoperative reductions in Glu and NE levels and concomitant elevations in GABA and 5-HT levels were observed at postoperative day 7. These findings suggest that, beyond its anatomic decompressive effects, microsurgical clot removal may facilitate restoration of neurotransmitter homeostasis at the molecular level, thereby improving neurological outcomes.

Glu and NE represent the principal excitatory neurotransmitters in the brain and are known to rise markedly following SICH, contributing to excitotoxicity, cerebral edema, blood–brain barrier disruption, and activation of inflammatory mediators. Elevated plasma Glu levels in SICH patients has been reported to be closely associated with early postoperative edema formation and poor prognosis (14), while other investigators have demonstrated that NE-mediated sympathetic overactivation exacerbates secondary brain injury (15). The significant reductions in Glu and NE levels observed in this study at postoperative day 7 implied that precise hematoma evacuation and mechanical decompression afforded by microsurgery may attenuate the persistent release of excitatory transmitters and inhibit secondary neuronal injury. These results align with those scholars who found that stereotactic clot evacuation reduced Glu levels and improved acute consciousness states (16), further underscoring the mechanistic importance of early surgical intervention in controlling excitotoxicity. By contrast, GABA and 5-HT are prototypical inhibitory neurotransmitters whose postoperative elevations may reflect activation of endogenous neuroprotective mechanisms that buffer excitotoxic damage and promote neural plasticity and reconnection. Activation of the 5-HT signaling pathway after intracerebral hemorrhage correlated with accelerated functional recovery (17), and GABA upregulation has been linked to reduced inflammatory mediators and preservation of eloquent cortex.

Subgroup analysis elucidated key clinical factors influencing surgical efficacy. Patients with hematoma volumes ≥30 mL exhibited higher Glu and NE levels and poorer outcomes, indicating that hematoma load directly impacts postoperative neurotransmitter metabolism and functional recovery. Larger bleeds produce more extensive tissue compression and destruction, triggering more severe Glu excitotoxicity and NE-related stress responses. This imbalance exacerbates secondary injury, disrupts neural network remodeling, and impairs long-term recovery. Conversely, smaller hematomas were associated with more moderate neurotransmitter shifts and better functional prognosis, suggesting hematoma volume as a critical predictor of postoperative metabolic re-equilibration and outcome. By hemorrhage location, the lobar group manifested the highest Glu and NE levels, lowest GABA and 5-HT levels, and a significantly lower GOS score compared with the thalamic group. The cerebral lobes, particularly frontal and temporal regions, subserve motor, language, and higher cognitive functions. Lobar hemorrhages, though less frequent than basal ganglia or thalamic bleeds, produce more direct cortical disruption and consequent deficits. The elevated excitatory (Glu and NE) and reduced inhibitory transmitter (GABA and 5-HT) profile indicated excessive local neuronal activation and dysregulation, underscoring the need for early intensive intervention and rehabilitation. Additionally, patients with moderate preoperative GCS scores (9–12) fared worst across multiple parameters, suggesting that moderate impairment may reflect a precarious balance between primary and secondary injury. This finding is not entirely consistent with the linear relationship between lower GCS scores and poorer prognosis reported in previous research (18). One possible explanation is that patients with moderate impairment (GCS 9–12) may not exhibit as severe a clinical presentation as those in deep coma (GCS 3–8), and therefore may not receive as prompt initiation of therapeutic interventions, while also lacking the relative stability observed in patients with mild impairment (GCS 13–15). Such patients may exist in a state of pathological compensation, during which cerebral edema and metabolic dysregulation progressively worsen, while excitatory neurotransmitter release remains elevated, and inhibitory neurotransmitter regulation is insufficient. In this “pre-decompensation” phase, disease progression may be misjudged or treatment delayed, predisposing these patients to postoperative extension of secondary injury and resulting in the poorest long-term neurological recovery.

mRS and GOS are standard tools for prognostic assessment, reflecting functional independence and global neurological recovery, respectively. At postoperative day 180, overall outcomes were favorable. Strong correlations were identified between postoperative day 7 neurotransmitter levels and long-term mRS and GOS scores, which suggested that microsurgical hematoma evacuation may facilitate the restoration of neurological function in elderly SICH patients, and that acute-phase alterations in neurotransmitter levels may serve as reliable predictors of long-term neurological recovery. Specifically, higher Glu and NE levels predicted higher mRS and lower GOS scores, whereas elevated GABA and 5-HT levels were associated with better outcomes. These correlations highlight the enduring impact of acute-phase neurochemical milieu on subsequent neural network remodeling and functional restoration. Excessive postoperative excitatory neurotransmission promotes calcium influx, mitochondrial dysfunction, and free-radical generation, exacerbating neuron loss and sustaining secondary injury (19, 20). Failure of timely reduction in their concentrations may portend ongoing tissue damage and compromised recovery. Previous animal study has similarly linked persistent Glu elevation with perihematomal metabolic disturbances and delayed apoptosis (21).

Conversely, GABA and 5-HT, as central inhibitory modulators, exert anti-excitotoxic, anti-inflammatory, and neuroplasticity-promoting effects. Patients exhibiting postoperative day 7 increases in GABA and 5-HT demonstrated significantly better 180-day functional recovery, indicating that activation of inhibitory pathways may create a permissive environment for tissue repair and network reconstitution. This observation concurs with reports of 5-HT-mediated axonal regeneration and functional improvement (22), and it supports exploration of GABAergic enhancement therapies in brain-injury rehabilitation. Thus, postoperative neurotransmitter profiling may serve not only as a biomarker of injury evolution but also as a potential target for tailored long-term interventions, such as early Glu/NE antagonists and GABA/5-HT augmenting agents, to optimize outcomes in elderly SICH patients. Although serum measurements cannot fully reflect central neurotransmitter dynamics due to the blood–brain barrier and peripheral metabolic influences, prior studies have shown meaningful correlations between serum and cerebrospinal fluid (CSF) levels of key neurotransmitters such as Glu and GABA in acute brain injury (23). Therefore, serum profiles may still provide clinically relevant insights into central neurochemical status and functional recovery.

Additionally, ROC analysis demonstrated that the combined neurotransmitter score robustly predicted poor neurological outcomes, with AUCs of 0.894 for mRS > 2 and 0.846 for GOS < 4, supporting its value as a prognostic biomarker.

This study has several limitations. First, as a single-center and prospective observational investigation with a limited sample size, the findings may not fully capture the heterogeneity of the broader patient population. Second, although serum neurotransmitter levels provide valuable insight into cerebral metabolic status, they cannot be assumed to directly mirror central nervous system neurotransmitter dynamics. Future studies should incorporate cerebrospinal fluid assays or metabolic neuroimaging modalities for validation. Third, postoperative interventions, such as rehabilitative therapy and pharmacological support, were not uniformly controlled, which may have introduced confounding effects on long-term functional outcomes. Fourth, although mRS scores at hospital discharge were systematically recorded, they were not included in detailed analysis. This decision was made to maintain consistency with the study’s primary objective—evaluating long-term neurological function at 180 days. Discharge mRS scores may be influenced by transient perioperative factors, variable hospital stay durations, and early complications, potentially limiting their ability to reflect true recovery status. By focusing on the 180-day mRS, the study aimed to provide a more stable and clinically meaningful assessment of functional outcome. Nevertheless, future studies incorporating serial mRS assessments at multiple early and late time points may offer a more comprehensive understanding of recovery trajectories following microsurgical hematoma evacuation.

Postoperative shifts in serum neurotransmitter levels, particularly elevated Glu and NE alongside reduced GABA and 5-HT, were consistently associated with poorer long-term neurological outcomes in this cohort. These associations remained evident across correlation and ROC analyses, suggesting that neurotransmitter profiles may reflect the underlying neurophysiological status after hematoma evacuation. While the present findings are limited by the absence of a non-surgical control group, they offer a basis for further investigation into the utility of serum neurotransmitters as adjunctive indicators in postoperative assessment and prognostic stratification.