Human platelet lysate: a potential therapeutic for intracerebral hemorrhage

Abstract

Intracerebral hemorrhage (ICH) is a major public health challenge worldwide, and is associated with elevated rates of mortality, disability, and morbidity, especially in low- and middle-income nations. However, our knowledge of the detailed molecular processes involved in ICH remains insufficient, particularly those involved in the secondary injury stage, resulting in a lack of effective treatments for ICH. Human platelet lysates (HPL) are abundant in bioactive factors, and numerous studies have demonstrated their beneficial effects on neurological diseases, including their anti-neuroinflammatory ability, anti-oxidant effects, maintenance of blood-brain barrier integrity, and promotion of neurogenesis. In this review, we thoroughly explore the potential of HPL for treating ICH from three critical perspectives: the rationale for selecting HPL as a treatment for ICH, the mechanisms through which HPL contributes to ICH management, and the additional measures necessary for HPL as a treatment for ICH. We elucidate the role of platelets in ICH pathophysiology and highlight the limitations of the current treatment options and advancements in preclinical research on the application of HPL in neurological disorders. Furthermore, historical developments and preparation methods of HPL in the field of biomedicine are discussed. Additionally, we summarize the bioactive molecules present in HPL and their potential therapeutic effects in ICH. Finally, we outline the issues that must be addressed regarding utilizing HPL as a treatment modality for ICH.

Keywords: bioactive factors; human platelet lysate; intracerebral hemorrhage; pathophysiology; treatment.

Figure 1

ICH pathophysiology. ICH, Intracerebral hemorrhage; PBI, primary brain injury; SBI, Secondary brain injury; ICP, intracranial pressure; BBB, blood–brain barrier. PBI: The growth of a hematoma causes compression of nearby blood vessels, which leads to ischemia and swelling in the adjacent brain tissue, along with a rise in intracranial pressure. SBI: neutrophils move into the hematoma region while resident immune cells, including microglia, activate and generate pro-inflammatory cytokines. Concurrently, erythrocytes from the hematoma are broken down, releasing hemoglobin and Fe2+. Collectively, these factors contribute to neuroinflammation and oxidative stress, which ultimately result in damage to the blood–brain barrier, exacerbating cerebral hematoma and inducing adjacent edema.

Figure 2

The role of platelets in ICH. BBB, blood–brain barrier; PNAs, platelet–neutrophil aggregates. Upon injury, platelets that have been activated attach to neutrophils through PSGL-1 and CD40, utilizing the surface receptors CD62P and CD40L, which leads to the development of PNAs. These aggregates enhance neutrophil function by releasing inflammatory mediators and cytokines. Moreover, neutrophils that are recruited, in conjunction with activated microglia and astrocytes, produce a range of pro-inflammatory substances, resulting in a cytokine storm that intensifies ICH. Conversely, bioactive factors present in the alpha granules of platelets may mitigate these pathological processes by reducing neuroinflammation, neuroapoptosis, and damage to the BBB.

Figure 3

NSCs, neural stem cells; ASCs, adipose-derived stem cells; BMSCs, Bone marrow mesenchymal stromal cells. Indirect application: HPL increases the efficiency of cell therapy in treating neurological disease by culturing various types of stem cells. Direct application: HPL allows bioactive factors to directly reach the injured site and exert therapeutic effects through intranasal or targeted administration.

Figure 4

(A) Brain slices obtained from representatives stained with TTC 24 h post-reperfusion in cases of stroke, both with and without intervention. (B) Assessment of infarct volumes quantitatively across various groups shows that the infusion of local human PRP lysate markedly decreases infarct volume in comparison to the group with no treatment for stroke (**p < 0.01). Additionally, a further decrease is observed when this group is compared to the other treatment groups (^#p < 0.05). The data is cited from a previous research (Zhang et al., 2015), this citation is permitted by the journal (License Number 5886510366832).

Figure 5

Synergistic role of bioactive molecules in HPL in the treatment of ICH. A: common elements in “antioxidant” and “antiapoptosis”: MANF, GPx, SOD, GAT; B: elements included exclusively in “neurogenesis”: EGF, TGF-β, PF4; C: elements included exclusively in “antiapoptosis”: GSN, MIR-126-3P; D: common elements in “antiapoptosis” and “neurogenesis”: PDGF, VEGF; E: elements included exclusively in “anti-inflammator”: FGF, IL-4; F: common element in “anti-inflammator” and “antiapoptosis”: IL-10; G: common element in “anti-inflammator,” “antiapoptosis” and “neurogenesis”: BNDF; H: common element in “anti-inflammator” and “neurogenesis”: IGF.